bluuebunny/crossref_metadata_2025 huggingface dataset:
Cholesterol Absorption, Synthesis, and LDL Metabolism in NIDDM
Authors: Gylling Helena , Miettinen Tatu A
Published: March 2007

OBJECTIVE

Cholesterol and lipoprotein metabolism was studied in mildly hypercholesterolemic nonobese men with NIDDM to find out which metabolic parameters regulate serum cholesterol level in these NIDDM subjects.

RESEARCH DESIGN AND METHODS

Nonobese NIDDM subjects (n = 13) and control subjects (n = 18) with serum cholesterol ≥ 6.0 and triglycerides ≤ 2.5 mmol/l were studied on a similar monoene-enriched diet. Cholesterol absorption was studied with peroral double isotopes and by measuring serum plant sterols with gas-liquid chromatography; cholesterol synthesis was studied by measuring sterol balance and by measuring serum cholesterol precursor sterols; and LDL kinetics was measured with 131I-labeled autologous apoprotein (apo) B.

RESULTS

Cholesterol absorption was significantly lower in NIDDM subjects than in the control subjects, as detected by low serum plant sterol levels and absorption percentage (23 vs. 29%, P < 0.05). Cholesterol synthesis was significantly higher in NIDDM subjects than in the control subjects, as detected by precursor sterols or balance data (18 vs. 12 mg · kg−1 · day−1, P < 0.01), cholesterol turnover (19 vs. 13 mg · kg−1 · day−1, P < 0.01), and LDL apo B removal (0.343 vs. 0.267 pools/day, P < 0.01). Serum total and LDL cholesterol levels were inversely correlated with cholesterol synthesis, which was positively related to the catabolism of LDL apo B and negatively related to cholesterol absorption efficiency.

CONCLUSIONS

In this small selected group of mildly hypercholesterolemic nonobese NIDDM subjects, the regulation of serum cholesterol levels was achieved by the homeostasis between cholesterol absorption, synthesis, and LDL fractional catabolism. Cholesterol turnover and removal of LDL apo B were high in NIDDM subjects, compared with the control subjects, whereas cholesterol absorption efficiency was abnormally low Because of the relatively small number of selected subjects, the present results are not directly applicable to the overall NIDDM population.
Total Plasma Antioxidant Capacity Predicts Thrombosis-Prone Status in NIDDM Patients
Authors: Ceriello Antonio , Bortolotti Nario , Pirisi Mario , Crescentini Adriana , Tonutti Laura , Motz Enrico , Russo Assunta , Giacomello Roberta , Stel Giuliana , Taboga Claudio
Published: March 2007

OBJECTIVE

To explore the hypothesis that a relationship exists between free radical activity and abnormalities in hemostasis in NIDDM.

RESEARCH DESIGN AND METHODS

The use of the total radical-trapping antioxidant parameter (TRAP) has very recently been proposed to explore the antioxidant property of a plasma and their mutual cooperation. In the present study, TRAP, vitamin E, vitamin C, vitamin A, uric acid, protein-bound SH (thiol) groups, fibrinogen, prothrombin fragments F1 + 2, and D-dimer have been evaluated in 46 NIDDM patients and 47 healthy matched control subjects.

RESULTS

In NIDDM patients, TRAP, vitamin A, SH groups, and uric acid were significantly reduced, whereas the level of vitamin E was significantly increased. Vitamin C was similar in the two groups. Fibrinogen, prothrombin fragment 1 + 2, and D-dimer were increased in diabetic patients. TRAP, but no single other antioxidant, had a strong inverse association with fibrinogen, prothrombin fragment 1 + 2, and D-dimer.

CONCLUSIONS

These findings are consistent with the hypothesis that oxidative stress may condition coagulation activation in diabetics. However, the data suggest that it is the total antioxidant capacity rather than any single plasma antioxidant that is the most relevant parameter.
Insulin Aspart in a 30/70 Premixed Formulation: Pharmacodynamic properties of a rapid-acting insulin analog in stable mixture
Authors: Weyer Christian , Heise Tim , Heinemann Lutz
Published: March 2007

OBJECTIVE

To study the pharmacodynamic properties of a 30/70 premixed formulation of the rapid-acting insulin analog insulin aspart (B28Asp) and its protamine-retarded preparation (30/70 IA) in comparison with a respective mixture of soluble human insulin and NPH insulin (30/70 HI).

RESEARCH DESIGN AND METHODS

In this single-center double-blind euglycemic glucose-clamp study, 24 healthy male volunteers (age, 26 ± 2 years; BMI, 23.7 ± 1.7 kg/m2) received single subcutaneous injections of 0.3 U/kg body wt of either 30/70 IA or 30/70 HI on 2 study days in randomized order. Glucose infusion rates (GIRs) were determined over a 24-h period after administration.

RESULTS

The injection of 30/70 IA resulted in an earlier onset and more pronounced peak of action (tmax, 127 ± 24 min; GIRmax 9.7 ± 2.3 mg · kg−1 · min−1) than 30/70 HI (tmax, 185 ± 52 min; GIRmax, 7.4 ± 1.7 mg · kg−1 · min−1_ (P < 0.001). The metabolic activity of 30/70 IA (measured as the sum of the glucose infused) within the first 4 h after injection was 37% > that of 30/70 HI (P < 0.0001), while the total metabolic potencies over 24 h of both preparations were comparable.

CONCLUSIONS

The 30/70 premixed formulation of insulin aspart shows a significantly greater metabolic effect in the first 4 h after subcutaneous injection than the 30/70 mixture of human insulin. Insulin aspart retains its pharmacodynamic properties in a premixed 30/70 formulation.
Phenotypic Expression of Diabetes Secondary to a T14709C Mutation of Mitochondrial DNA: Comparison with MIDD syndrome (A3243G mutation): a case report
Authors: Vialettes B H , Paquis-Flucklinger V , Pelissier J F , Bendahan D , Narbonne H , Silvestre-Aillaud P , Montfort M F , Righini-Chossegros M , Pouget J , Cozzone P J , Desnuelle C
Published: March 2007

OBJECTIVE

To analyze the clinical and biochemical features of a recently described point mutation of mitochondrial DNA associated with diabetes. This mutation, characterized by a T14709C transition of a highly conserved nucleotide in the region coding for the glutamic acid tRNA, is heteroplasmic.

RESEARCH DESIGN AND METHODS

The phenotypic expression in the insulin-requiring diabetic proband from the pedigree was compared to that of diabetic probands from three families with the classic A3243G mtDNA mutation (maternally inherited diabetes and deafness [MIDD] syndrome). The same investigations to evaluate pancreatic neurosensorial and muscle involvement were performed in all four patients.

RESULTS

The natural courses of the diabetes and the hearing defects were not different between the two mutations. The patient with the 14,709 mutation, however, exhibited a milder alteration of pigmentary epithelium of retina and a much more severe muscle involvement, as attested by the clinical expression and the concurrent anomalies of muscle energy production evidenced by 31P magnetic resonance spectroscopy, confirming the profound impairment of oxidative processes.

CONCLUSIONS

This novel mutation has to be added to the other known mtDNA anomalies in order to ascribe some diabetes suspected to arise from mitochondrial defects to this nosological framework.
Visceral Fat and Cardiovascular Risk Factors in Chinese NIDDM Patients
Authors: Anderson Patricia J , Chan Juliana C N , Chan Y L , Tomlinson Brian , Young Robert P , Lee Zoe S K , Lee Kenneth K C , Metreweli Constantine , Cockram Clive S , Critchley Julian A J H
Published: March 2007

OBJECTIVE

The interrelations between obesity, glucose intolerance, hypertension, dyslipidemia, and insulin resistance are well recognized. These relationships are of particular interest in Hong Kong's Chinese population, in whom increasing affluence has coincided with a marked increase in the prevalence of NIDDM. We designed a pilot study to examine the relationships between visceral fat and cardiovascular risk factors in Chinese NIDDM patients.

RESEARCH DESIGN AND METHODS

We studied 21 Chinese NIDDM patients whose visceral fat was quantified by magnetic resonance imaging. Cardiovascular risk factors including plasma lipids and 24-h ambulatory blood pressure (BP) were measured. In addition, insulin resistance was determined by a short insulin tolerance test (SITT).

RESULTS

Increased visceral adiposity was significantly correlated with plasma triglycerides (r = 0.63, P = 0.004), the total cholesterol/HDL cholesterol ratio (r = 0.61, P = 0.008), the urinary albumin/creatinine ratio (r = 0.49, P = 0.04), and decreased insulin sensitivity as measured by the SITT (r = 0.47, P = 0.03). When the data were analyzed by tertiles, increasing visceral fat area was associated with higher plasma triglycerides, lower HDL cholesterol, and a smaller plasma glucose decrement during the SITT. In addition, the diurnal rhythm in BP and heart rate tended to be best preserved in those with the least visceral obesity.

CONCLUSIONS

This pilot study demonstrates that visceral fat accumulation is associated with dyslipidemia, hypertension, insulin resistance, and albuminuria in Chinese patients with NIDDM.
Nighttime Insulin Kinetics and Glycemic Control in Type 1 Diabetes Patients Following Administration of an Intermediate-Acting Lispro Preparation
Authors: Janssen Maureen M J , Casteleijn Sandrina , Devillé Walter , Popp-Snijders Corrie , Roach Paris , Heine Robert J
Published: March 2007

OBJECTIVE

To determine insulin kinetics and overnight glycemic control after bedtime administration of a new intermediate-acting insulin preparation called neutral protamine lispro (NPL).

RESEARCH DESIGN AND METHODS

We studied 12 patients with well-controlled type 1 diabetes. The study had a double-blind, randomized, crossover design. After a lead-in period of 10–14 days two experiments were carried out with an interval of 2–7 days. During these experiments overnight insulin kinetics and fasting blood glucose levels were studied after evening administration of NPH insulin and NPL. Blood glucose levels < 3.8 mmol/l were treated by means of a variable infusion of a 20% glucose solution.

RESULTS

A trend toward a shorter time to peak insulin concentration was observed after administration of NPL (P = 0.07). No differences between NPH and NPL were detected in the total area under the curve (AUC) for insulin, in insulin levels before breakfast, or in glucose levels before breakfast (P = 0.5, 0.6, and 0.4, respectively).

CONCLUSIONS

We detected no major differences between NPH and NPL in the total AUC for insulin, prebreakfast glucose levels, or prebreakfast insulin levels. Therefore, we conclude that NPH and NPL are equally effective in controlling overnight glycemia.
Cancer Arising After Pancreas and/or Kidney Transplantation in a Series of 99 Diabetic Patients
Authors: Martinenghi Sabina , Dell'Antonio Giacomo , Secchi Antonio , Carlo Valerio Di , Pozza Guido
Published: March 2007

OBJECTIVE

Recipients of solid organ transplants have an increased risk of developing certain types of malignancies as compared with the general population. The majority of the literature has reported on neoplasms in kidney and heart transplant recipients.

RESEARCH DESIGN AND METHODS

We describe 9 neoplasms occurring in 7 out of 73 IDDM patients after simultaneous pancreas and kidney transplantation. No cases were recorded among 26 IDDM recipients of kidney transplantation.

RESULTS

Among the neoplasms found were 2 cases of posttransplant lymphoproliferative disorder (PTLD), malignant melanoma, basal-cell and squamous-cell carcinoma of the skin in the same patient, squamous-cell carcinoma in situ of the vulva, hepatocarcinoma, small-cell lung cancer, and ductal carcinoma of the breast. Four patients died. Among immunological risk factors, over-immunosuppression for steroid-resistant kidney rejection was administered only in the 2 cases of PTLD.

CONCLUSIONS

Increased dosage of immunosuppressive agents may be necessary in some patients of prevent or treat rejection in view of their reduced survival on hemodialysis.
IDDM and Early Infant Feeding: Sardinian case-control study
Authors: Meloni Tullio , Marinaro Anna Maria , Mannazzu Maria Chiara , Ogana Augusto , Vecchia Carlo La , Negri Eva , Colombo Carla
Published: March 2007

OBJECTIVE

To further investigate the association between the type of feeding in infancy and the development of IDDM.

RESEARCH DESIGN AND METHODS

We have carried out a case-control study in the area of Sassari (northern Sardinia, Italy), which is characterized by an ethnically homogenous population at high risk of IDDM. The study subjects comprised 100 IDDM patients and 100 control subjects, matched for sex and age and selected from children admitted at the Department of Pediatrics of the University of Sassari. Diabetic children (53 boys, 47 girls) had been diagnosed between 1983 and 1994, and their age at diagnosis ranged between 1 and 15 years. Information on feeding patterns during the 1st year of life was collected through questionnaires administered to the mothers. The questionnaire was designed to evaluate the duration of complete or partial breast-feeding and the age at which dietary products containing cow's milk were introduced into the diet.

RESULTS

A larger proportion of the diabetic children rather than the control children had been breast-fed, and the risk of IDDM among children who had not been breast-fed was below unity (odds ratio [OR] 0.41; 95% CI 0.19–0.91). No clear difference was observed between diabetic and control subjects in the duration of breast-feeding (medians: 3 and 2 months, respectively), even if, overall, the data suggested a slight increase in the risk of IDDM with longer duration of breast-feeding (OR 1.10; 95% CI 0.99–1.22 per month). Although a larger proportion of control children rather than diabetic children had been given cow's milk–derived formula and solid food before the age of 3 months, there was no time-risk relationship.

CONCLUSIONS

Our data do not support the existence of a protective effect of breast-feeding on the risk of IDDM, nor do the data indicate that early exposure to cow's milk and dairy products has any influence on the development of IDDM in a high-risk population.
Is Type II Diabetes Associated With an Increased Risk of Cognitive Dysfunction?: A critical review of published studies
Authors: Strachan Mark W J , Deary Ian J , Ewing Fiona M E , Frier Brian M
Published: March 2007

Type II (non-insulin-dependent) diabetes may be associated with impaired cognitive function. A detailed search of the literature has identified 19 controlled studies in which cognitive function in type II diabetes has been examined. The studies vary widely with respect to the nature of the diabetic populations studied and the psychological tests used. Thirteen studies demonstrated that the diabetic individuals performed more poorly in at least one aspect of cognitive function. The most commonly affected cognitive ability was verbal memory. Psychomotor ability and frontal lobe function were affected less consistently. The remaining six studies showed no differences in cognitive ability between subjects with type II diabetes and nondiabetic control subjects, but none had adequate statistical power to detect a between-group difference in cognitive ability of 0.5 of a standard deviation (a medium effect size). These findings are consistent with type II diabetes being associated with an increased risk of cognitive dysfunction. However, the widespread differences in methodology between the studies should lead to a cautious interpretation of their conclusions. The etiology of any cognitive decrement in type II diabetes is likely to result from an interaction between metabolic abnormalities intrinsic to diabetes, diabetes-specific complications, and other diabetes-related disorders.
Performance of an NIDDM Screening Questionnaire Based on Symptoms and Risk Factors
Authors: Ruige Johannes B , Neeling J Nico D de , Kostense Pieter J , Bouter Lex M , Heine Robert J
Published: March 2007

OBJECTIVE

To investigate to what extent a short questionnaire on symptoms and risk factors can be used to identify people at increased risk for undiagnosed NIDDM.

RESEARCH DESIGN AND METHODS

A general population sample of 2,364 Caucasian subjects, age 50–74 years, not known to have diabetes, completed a questionnaire on diabetes-related symptoms and risk factors. Subsequently, they underwent an oral glucose tolerance test. A backward stepwise multiple logistic regression was carried out with the absence or presence of newly detected diabetes as the dependent variable and the items from the questionnaire as the independent variables. The selected items were included in a new symptom risk questionnaire, which was evaluated in a different population sample of 786 subjects, age 45–74 years, not known to have diabetes and compared with existing questionnaires.

RESULTS

The newly developed symptom-risk questionnaire contains questions concerning the following items, which were independently and significantly (P < 0.05) associated with the presence of previously undiagnosed diabetes: pain during walking with need to slow down, shortness of breath when walking with people of the same age, frequent thirst, age, sex, obesity, parent or sibling with diabetes, use of antihypertensive drugs, and reluctance to use a bicycle for transportation. The 1993 American Diabetes Association questionnaire, the 1995 Herman et aL (17) questionnaire, and the newly developed symptom-risk questionnaire had sensitivities of 59, 72, and 72%; specificities of 57, 55, and 56%; positive predictive values of 5.6, 6.4, and 6.5%; and negative predictive values of 97, 98, and 98%, respectively.

CONCLUSIONS

The newly developed symptom-risk questionnaire has good performance characteristics, and the advantage of a variable cutoff makes it a useful screening tool for NIDDM in general practice.
Clustering of Childhood IDDM: Links with age and place of residence
Authors: Law Graham R , McKinney Patricia A , Staines Anthony , Williams Rhys , Kelly Mike , Alexander Freda , Gilman Estelle , Bodansky H Jonathan
Published: March 2007

OBJECTIVE

To improve understanding of the etiology of IDDM by analyzing spatial and space-time distribution of the incidence in children.

RESEARCH DESIGN AND METHODS

Statistical tests to detect clustering were applied to a population-based register of 1,490 children (aged 0–16 years) with IDDM in Yorkshire, northern England. The Knox test analyzed clustering in space and time, and the Potthoff-Whittinghill test quantified spatial differences in incidence between small-area census units (electoral wards). The Potthoff-Whittinghill test was conditioned for childhood population density and deprivation (Townsend index).

RESULTS

Both tests demonstrated clustering of IDDM in Yorkshire children. Space-time and spatial clustering is strongest in the younger children (0–4 and 5–9 years of age), even after conditioning for known associations. Clustering was more common in the county of Humberside during the years 1982–1985 and in wards of low population density (< 0.26 0- to 16 year-old subjects per hectare).

CONCLUSIONS

The study revealed a nonrandom space-time distribution of IDDM in children not accounted for by known covarying demographic factors. The Potthoff-Whittinghill test has not previously been applied to childhood IDDM. The new finding of strong clustering in young children is consistent with early exposure, possibly in utero, to infectious agents or localized environmental sources.
Carotid Atherosclerosis and Serum Lipoprotein(a) Concentrations in Patients With NIDDM
Authors: Yamamoto Maki , Egusa Genshi , Yamakido Michio
Published: March 2007

OBJECTIVE

To investigate the association of carotid atherosclerosis and serum lipoprotein(a) [Lp(a)] concentrations in subjects with NIDDM.

RESEARCH DESIGN AND METHODS

We measured carotid intima-media thickness (IMT) and Lp(a) concentrations in 117 NIDDM subjects. Subjects were divided into tertiles according to IMT values and number of plaques.

RESULTS

Serum Lp(a), but not lipid and apoprotein levels, increased significantly with increasing IMT (20.0 ± 2.3, 24.7 ± 3.3, and 39.8 ± 4.3 mg/dl [mean ± SE], respectively, P < 0.001). Serum Lp(a) increased with increasing number of plaques (18.4 ± 2.5 mg/dl in 59 subjects with no plaques, 25.8 ± 2.5 mg/dl in 24 subjects with 1 plaque, and 38.7 ± 5.1 mg/dl in 34 subjects with more than 1 plaque; P < 0.05). Furthermore, the mean IMT and Lp(a) levels in the subjects with cerebrovascular disease (CD) were significantly higher than in those without CD (1.25 ± 0.04 mm and 41.2 ± 4.7 mg/dl vs. 1.08 ± 0.03 mm and 22.2 ± 1.9 mg/dl; P < 0.005). The mean IMT and Lp(a) levels were higher in subjects with ischemic heart disease (IHD) than in those without IHD, although statistical significance was not observed (1.21 ± 0.06 mm and 31.7 ± 4.7 mg/dl vs. 1.10 ± 0.03 mm and 27.0 ± 2.4 mg/dl, respectively).

CONCLUSIONS

Elevated serum Lp(a) concentrations are associated with carotid atherosclerosis in NIDDM subjects.
Validity of Screening for Individuals at Risk for Type I Diabetes by Combined Analysis of Antibodies to Recombinant Proteins
Authors: Christie Michael R , Roll Ursula , Payton Mark A , Hatfield Emma CI , Ziegler Anette-G
Published: March 2007

OBJECTIVE

To determine whether screening for the presence of multiple antibody markers for IDDM is effective at identifying individuals with high risk for disease development.

RESEARCH DESIGN AND METHODS

Antibodies to GAD and the tyrosine phosphatase-like protein IA-2 were determined in sequential serum samples from 44 first-degree relatives of IDDM patients, identified as possessing islet cell antibody (ICA) and/or insulin autoantibody (IAA), who were followed prospectively for IDDM development, ICA, IAA, and antibodies to GAD and IA-2 were also determined in 93 cases of new-onset nonfamilial IDDM.

RESULTS

The presence of two or more antibodies in addition to ICA or IAA conferred high risk (61%) for development of IDDM within 5 years of entry into the study and identified 89% of those who have developed IDDM on current follow-up. None of the relatives positive for ICA or IAA alone, in the absence of other antibody markers, have developed IDDM. Antibodies to islet antigens could both appear and disappear in follow-up samples obtained after entry into the study. The majority (60%) of young (< 16 years), sporadic cases of IDDM had multiple antibodies to islet antigens, but this proportion was lower in older patients (37%).

CONCLUSIONS

A screening strategy based on the analysis of antibodies to multiple islet antigens can predict IDDM at high sensitivity and specificity in families, and such a strategy may also be applicable to identify young individuals in the general population with high disease risk. Since appearance of antibodies to different antigens occurs sequentially rather than simultaneously, accurate assessment of diabetes risk based on the presence of multiple antibodies will require follow-up over a number of years after the first evidence of islet autoimmunity.
Determinants of Growth in Diabetic Pubertal Subjects
Authors: Zachrisson I , Brismar K , Hall K , Wallensteen M , Dahlqvist G
Published: March 2007

OBJECTIVE

To analyze the relationship among metabolic control, IGF-I, and growth in pubertal diabetic subjects.

RESEARCH DESIGN AND METHODS

In 72 diabetic children, we have studied the pattern of change of IGF-I, IGF-I SD score, IGF binding protein (BP)-1, and growth rate in different pubertal stages and have analyzed their relation to age sex, weight/length index, HbA1c, insulin concentration, insulin dose, and dehydroepiandrosteronesulfate (DHEAS).

RESULTS

The serum IGF-I values increased up to Tanner stage 4 and thereafter decreased, whereas IGFBP-1 showed the inverse pattern. When transforming the IGF-I values into SD scores, correcting for age, sex, and pubertal stage, it was shown that the deviation from normal values increased with increasing pubertal stage in boys, but was equal in stages 3–5 in girls. Using multiple regression analysis, HbA1c, insulin dose, and DHEAS were significantly correlated to IGF-I SD score (R2 = 0.253, P = 0.001). IGFBP-I levels in the afternoon were within normal range. LogIGFBP-1 showed an inverse correlation, to insulin concentration in single correlation (r = −0.26, P = 0.02). In single correlation, growth rate correlated significantly to insulin dose (r = 0.25, P = 0.03). In a multiple regression analysis, only DHEAS and IGF-I SD score were found to be significantly correlated to growth rate (R2 = 0.370, P < 0.001). The 18 adolescents who had reached their final height did not deviate from their target final height, according to their recorded growth since birth.

CONCLUSIONS

In a group of fairly well-controlled diabetic children, the normal increase in IGF-I during puberty is blunted. Despite decreased IGF-I levels, target final height was attained, probably because of adequate insulin compensation leading to normal IGFBP-l, thus adequate bioavailability of IGF-I. Our results point out the importance of sufficient exogenous insulin in the period of rapid linear growth.
Long-Term Follow-Up of Diabetes in Two Patients With Thiamine-Responsive Megaloblastic Anemia Syndrome
Authors: Valerio Giuliana , Franzese Adriana , Poggi Vincenzo , Tenore Alfred
Published: March 2007

OBJECTIVE

To describe a 15-year follow-up of diabetes and to present data regarding pancreatic β-cell function in two adolescents affected by the thiamine-responsive megaloblastic anemia (TRMA) syndrome.

CASE REPORTS

The first patient (PMR) is a 17.5-year-old Italian girl who presented megaloblastic anemia at 7.5 months of age. At age 2.5 years, because of the presence of diabetes and sensorineural deafness, she was diagnosed with TRMA syndrome and started treatment with thiamine-HCl, followed very early by benzoyloxymethyl-thiamine (BOM-T). The second patient (PF) is a 16.8-year-old Italian boy born to consanguineous parents. Sensorineural deafness was diagnosed at age 1.5 years, while diabetes with ketoacidosis and megaloblastic anemia were diagnosed at age 3 years. Treatment with thiamine HCl was started immediately after diagnosis and changed to BOM-T 2 months later. Subsequent to the initiation of the vitamin, the two patients did not require insulin for ∼ 7 and 10 years, respectively. Puberty was determinant in deteriorating the metabolic control in these patients, leading to treatment with an oral hypoglycemic agent and finally to a reinstitution of insulin therapy.

CONCLUSIONS

The hormonal assessment in our patients (normal insulin response to oral glucose in childhood, preserved C-peptide secretion in case 2) and the good response to an oral hypoglycemic agent would indicate that the pancreatic disease may initiate as type 2 diabetes and may progress after several years to an insulin-requiring diabetes, as indicated by the exhaustion of the insulin secretory capacity.
Comparison of GAD and ICA512/IA-2 Antibodies at and After the Onset of IDDM
Authors: Yokota Ichiro , Matsuda Junko , Naito Etsuo , Ito Michinori , Shima Kenji , Kuroda Yasuhiro
Published: March 2007

OBJECTIVE

Longitudinal changes in GAD antibody (Ab) and ICA512/IA-2 (ICA512) Ab were examined in relation to age at the onset of diabetes and autoimmunity against the thyroid gland.

RESEARCH DESIGN AND METHODS

GADAb, ICA512Ab, and antithyroid autoantibody were examined at onset in 40 juvenile-onset IDDM patients (17 males, 23 females, age at onset 9.4 ± 4.1 years, range 1.7−20). To assess the changes in antibody levels, 29 patients were followed up with sequential serum samples for up to 5 years.

RESULTS

At onset, GADAb, ICA512Ab, and antithyroid autoantibody (thyroglobulinAb or thyroid peroxidaseAb) were found in 70, 58, and 25% of the 40 patients, respectively. Prepubertal patients (n = 21) had a significantly higher prevalence and index of ICA512Ab compared with pubertal patients (n = 19) (76 vs. 37%, P = 0.012, and 2.43 ± 2.36 vs. 0.66 ± 1.23, P = 0.011), while GADAb was more prevalent in pubertal patients (57 vs. 84%, P = 0.09). A longitudinal analysis of GADAb and ICA512Ab showed that GADAb levels declined more slowly than those of ICA512Ab (P = 0.008). Patients with continuous extremely high levels of GADAb also had high levels of antithyroid autoantibody.

CONCLUSIONS

The measurement of ICA512Ab is useful in prepubertal patients, who often show rapid progression of the disease. The presence of autoimmunity against thyroid gland seems to influence the GADAb level but not the ICA512Ab level.
Counterregulatory Hormone Responses After Long-Term Continuous Subcutaneous Insulin Infusion With Lispro Insulin
Authors: Tsui Elaine Y L , Chiasson Jean-Louis , Tildesley Hugh , Barnie Annette , Simkins Sari , Strack Thomas , Zinman Bernard
Published: March 2007

OBJECTIVE

To determine whether the long-term use of insulin lispro (LP) affects the counterregulatory hormone response to hypoglycemia.

RESEARCH DESIGN AND METHODS

Ten patients (age range 26-51 years; ratio of men to women 9:1; BMI 24.9 ± 0.48; mean HbA1c 7.84 ± 0.25%) with IDDM, treated with continuous subcutaneous insulin infusion (CSII; Disetronic H-TRON V100) were studied using a double-blind, crossover design. Patients were randomized to LP or human regular insulin (HR) for 3 months and then crossed over to the other insulin for an additional 3 months. All meal boluses were given 0-5 min before breakfast, lunch, and dinner. Counterregulatory hormone responses to a stepped hypoglycemic clamp (consecutive glucose levels in mmol/l: 4.2; 3.5; 2.8, each for 1 h) were evaluated at the end of each treatment period.

RESULTS

HbA1c was significantly lower with LP versus HR (7.47 ± 0.28% vs. 7.9 ± 0.26%, P = 0.04). The incidence of hypoglycemia per 30 days (capillary blood glucose < 3.0 mmol/l and/or symptoms) during the last month of the study was significantly lower with LP versus HR (8.7 ± 2.9 vs. 11.8 ± 2.9, P = 0.03). The total daily insulin dosage was not different in the two treatment periods. There was no episode of severe hypoglycemia or diabetic ketoacidosis. The peak growth hormone, cortisol, glucagon, and epinephrine responses during the same period of hypoglycemia were not different for each treatment period.

CONCLUSIONS

The use of LP in CSII results in improved glycemic control and a decrease in the frequency of hypoglycemia without adversely affecting counterregulatory hormone response to hypoglycemia.
Glycemic Control Is Related to the Electrophysiologic Severity of Diabetic Peripheral Sensorimotor Polyneuropathy
Authors: Tkac Ivan , Bril Vera
Published: March 2007

OBJECTIVE

The aim of the present study was to examine risk factors for the electrophysiologic severity of diabetic peripheral sensorimotor polyneuropathy (DSP).

RESEARCH DESIGN AND METHODS

A total of 97 patients with type 1 diabetes (25 patients) or type 2 diabetes (72 patients) were included in this cross-sectional study. Nerve conduction studies (NCS) were performed on median motor and sensory nerves, peroneal motor nerve, and both sural nerves. The severity of DSP was expressed as the sum of nerve conduction velocities (SNCV) and the score of distal amplitudes (SAMP) of the above-mentioned nerves. General linear models were used to assess the relationship between overall severity of DSP, as well as the severity of lower extremity, upper extremity, motor nerve, or sensory nerve involvement and various risk factors.

RESULTS

GHb was significantly related to both SNCV and SAMP in univariate and multivariate regression analyses. This relationship was present in models where GHb was handled either as a continuous variable or as a categorical variable with highest significance level, with a GHb cutoff level of 9%. The difference in NCV for individual nerves in patients with good-to-moderate glycemic control (GHb ≤9%) and those with poor glycemic control (GHb ≥9%) ranged from 1.8 to 3.6 m/s. SAMP was also significantly lower in patients with poor control. SNCV was also significantly related in multivariate analysis to duration of diabetes and height, while SAMP was related to duration of diabetes, age, and male sex.

CONCLUSIONS

The severity of DSP expressed by electrophysiologic criteria was significantly related to glycemic control in a study including patients with type 1 or type 2 diabetes. Based on the results of the present study, it might be predicted that better diabetic control would decrease the severity of DSP
Association of hormone replacement therapy and carotid wall thickness in women with and without diabetes.
Authors: Dubuisson J T , Wagenknecht L E , D'Agostino R B , Haffner S M , Rewers M , Saad M F , Laws A , Herrington D M
Published: March 2007

OBJECTIVE: Atherosclerosis is the major underlying cause of death for women with type 2 diabetes. We examined the relationship between use of postmenopausal hormone replacement therapy(HRT) and subclinical atherosclerosis among women with type 2 diabetes, impaired glucose tolerance (IGT), and normal glucose tolerance. RESEARCH DESIGN AND METHODS: A cross-sectional analysis was conducted among 623 postmenopausal women in the Insulin Resistance Atherosclerosis Study (IRAS). Current users of HRT, n = 200, were compared with 104 former users and 319 never users. Intimal-medial wall thicknesses (IMTs) of the common carotid (CCA) and internal carotid (ICA) arteries were used as measures of atherosclerosis. RESULTS: Significant differences between HRT user groups were noted for certain demographic, socioeconomic, and lifestyle factors. After adjustment for these and other coronary heart disease risk factors, current users had a 69 microm thinner ICA IMT than never users (P = 0.06). Former users had a 96 pm thinner ICA IMT than never users (P = 0.03). No significant difference was observed for the CCA. Although women with type 2 diabetes had thicker carotid IMT than women without diabetes, the association between HRT use and thinner IMT was similar in both groups. The difference between current and never users was attenuated by adjustment for HDL and LDL cholesterol. Neither duration of HRT use nor HRT regimen was associated with IMT in either artery. CONCLUSIONS: This analysis suggests that current and former use of HRT is associated with reduced atherosclerosis and that women with type 2 diabetes may receive the same benefit from HRI as women without diabetes.
The Diabetes in Early Pregnancy Study: beta-hydroxybutyrate levels in type 1 diabetic pregnancy compared with normal pregnancy. NICHD-Diabetes in Early Pregnancy Study Group (DIEP). National Institute of Child Health and Development.
Authors: Jovanovic L , Metzger B E , Knopp R H , conley M R , Park E , Lee Y J , Simpson J L , Holmes L , Aarons J H , Mills J L
Published: March 2007

OBJECTIVE: The objective was to assess relationships between beta-hydroxybutyrate (beta-OHB) level and pregnancy outcome in human pregnancy in light of the fact that high levels of beta-OHB cause malformations and growth retardation in in vitro studies. RESEARCH DESIGN AND METHODS: We analyzed beta-OHB in prospectively collected specimens from the National Institute of Child Health and Human Development-Diabetes in Early Pregnancy Study, in gestational weeks 6-12 in diabetic (n = 204-239) and nondiabetic (n = 316-332) pregnant women. RESULTS: Levels of beta-OHB in diabetic women were 2.5-fold higher than in nondiabetic pregnant women at 6 weeks' gestation and declined to 1.6-fold above nondiabetic women by 12 weeks' gestation (P < 0.0001 at all times). beta-OHB was positively correlated with glucose levels (P < 0.0001) in diabetic mothers, probably reflecting degree of diabetic control. beta-OHB correlated inversely with glucose (P < 0.0003) (gestational week 6 only) in nondiabetic mothers, possibly reflecting caloric intake. beta-OHB tended to be lower (not higher) in diabetic and nondiabetic mothers with malformed infants or pregnancy losses, but the difference was not statistically significant. beta-OHB in diabetic mothers at 8, 10, and 12 weeks correlated inversely with birth weight (P = 0.004-0.02), even after adjusting for maternal glucose levels. beta-OHB levels were also generally lower in diabetic mothers of macrosomic infants, and week 12 ultrasound crown-rump measurements were inversely related to beta-OHB levels. CONCLUSIONS: The lst trimester beta-OHB is significantly higher in diabetic than nondiabetic pregnant women. In both groups, beta-OHB tended to be lower, not higher, in mothers who had a malformed infant or pregnancy loss. beta-OHB was inversely related to crown-rump length and birth weight. The modest beta-OHB elevation in the 1st trimester of reasonably well-controlled diabetic pregnancy is not associated with malformations, probably because beta-OHB levels causing malformations in embryo culture models are 20- to 40-fold higher. The mechanism of the beta-OHB association with impaired fetal growth is unknown.
Prescription Drug Use and Costs Among Diabetic Patients in Primary Health Care Practices in Germany
Authors: Rathmann Wolfgang , Haastert Burkhard , Roseman Jeffrey M , Gries F Arnold , Giani Guido
Published: March 2007

OBJECTIVE

To evaluate drug prescriptions and costs among diabetic patients in primary care practices in Germany.

RESEARCH DESIGN AND METHODS

Computerized data on prescriptions and costs (drug company sales prices) were analyzed in 30,604 diabetic and 17,723 (5% random sample) nondiabetic patients from 362 primary care practices during 1994. Relative use ratios for drug groups were obtained from logistic regression models (odds ratio [OR] for diabetes) controlling for age, sex, and other covariates. Relative costs (diabetic:nondiabetic) were estimated by direct age and sex standardization.

RESULTS

Diabetic patients had an increased prescription use for most drugs. A substantial increased use (OR ≥ 1.4) was found for cardiovascular drugs, fibrates, gout medication, laxatives, and wound care products. Diabetic subjects (7.9% of all patients) accounted for 21% of total annual prescription costs in the practices. Total costs (U.S. dollars) per patient-year were threefold higher (diabetic patients $384; control subjects $123). After excluding antidiabetic agents and age- and sex-standardization, relative costs were still 1.5 times higher (P < 0.05). Diabetes treatment accounted for 24% of total costs in diabetic patients (insulin 12%; oral antidiabetics 6%). The most important cost factor was cardiovascular drugs (CVDs) (39%). Three CVD groups accounted for about 50% of total CVD costs in diabetic patients (ACE inhibitors 25%; Ca-antagonists 16%; nitrates 10%).

CONCLUSIONS

Prescription use among diabetic patients in primary health care practices was predominantly increased for cardiovascular drugs and for treatment of diabetes-associated disorders. Diabetic patients accounted for over one-fifth of the total pharmacy costs in primary practices, indicating that diabetes is a major economic factor in drug use.
Gastric Emptying Delay and Gastric Electrical Derangement in IDDM
Authors: Cucchiara Salvatore , Franzese Adriana , Salvia Gennaro , Alfonsi Lucia , Iula Vita D , Montisci Antonella , Moreira Flavio L
Published: March 2007

OBJECTIVE

Patients with diabetes can develop gastrointestinal motor complications; however, prevalence of gut dysmotility in children with diabetes is poorly understood. We measured gastric emptying time and gastric electrical activity in children with IDDM; presence of dyspeptic symptoms was also assessed.

RESEARCH DESIGN AND METHODS

Gastric emptying time and gastric electrical activity were measured by ultrasonography and electrogastrography (EGG), respectively, in 40 consecutive IDDM children (median age: 9 years [6–14]) without autonomic neuropathy; 15 healthy children (median age: 7 years [4–15]) served as control subjects. The EGG variables studied were percent of electrical dysrhythmias (bradygastria or 0.5−2.0 cpm, tachygastria or 4.0–9.0 cpm; normal rhythm is 2.0–4.0 cpm) and fed-to-fasting ratio of the dominant EGG power. Blood glucose level in the fasting state and 180 min after feeding and HbA1C concentration were also measured. Data are given as median (ranges) and means ± SD. Statistical analysis was performed using the parametric t test and the nonparametric signed-rank tests, with P < 0.05 considered significant.

RESULTS

Gastric emptying time was delayed in 26 patients (group A), whereas in 14 patients (group B), it was in the same range as control values; group A patients significantly differed from group B for increased prevalence of gastric electrical dysrhythmias (P < 0.01) and for a lower fed-to-fasting ratio of the dominant EGG power (P < 0.01). Group B patients did not differ from control subjects for the EGG variables measured. Diabetic children with gastroparesis had significantly higher levels of both HbA1C and blood glucose measured 180 min after feeding than those with normal gastric emptying time (P < 0.05); there was a significant correlation between levels of HbA1C and degree of gastric emptying delay, whereas a significant inverse correlation between gastric emptying time and fed-to-fasting ratio of the dominant EGG power was found both in patients and control subjects.

CONCLUSIONS

Delay of gastric emptying time and gastric electrical abnormalities are found in a high proportion of children with diabetes and can contribute to poor glycemic control, most likely by causing a mismatch between the onset of insulin action and the delivery of nutrients into the small intestine. Diabetic children with unexplained poor glycemic control should be investigated for abnormalities in gastric motility.
Beginning Insulin Treatment of Obese Patients With Evening 70/30 Insulin Plus Glimepiride Versus Insulin Alone
Authors: Riddle Matthew C , Schneider Jill ,   The Glimepiride Combination Group
Published: March 2007

OBJECTIVE

This study tested a simple algorithm for beginning insulin for obese patients with type 2 diabetes after sulfonylurea failure, comparing suppertime 70/30 insulin plus continued glimepiride with insulin alone.

RESEARCH DESIGN AND METHODS

This was a multicenter ambulatory randomized double-masked parallel comparison. There were 208 subjects with secondary failure to sulfonylureas who took glimepiride titrated to 8 mg b.i.d. for 8 weeks; 145 subjects with fasting plasma glucose (FPG) 180–300 mg/dl (10–16.7 mmol/1) on this treatment were randomized to placebo plus insulin (PI) or glimepiride plus insulin (GI) for 24 weeks. A dosage of 70/30 insulin before supper was titrated, seeking fasting capillary blood glucose (FBG) 120 mg/dl (6.7 mmol/1), equivalent to FPG 140 mg/dl (7.8 mmol/1). Outcome measures included FPG, HbA1c, insulin dosage, weight, serum insulin and lipids, and adverse events.

RESULTS

FPG and HbA1c were equivalent at baseline: 261 vs. 250 mg/dl (14.5 vs. 13.9 mmol/1), and 9.9 vs. 9.7%. At 24 weeks, the FPG target was achieved in both groups (136 vs. 138 mg/dl, 7.6 vs. 7.6 mmol/1), and HbA1c values were equal (7.7 vs. 7.6%). However, with GI, control improved faster and fewer subjects dropped out (3 vs. 15%, P < 0.01), and less insulin was needed (49 vs. 78 U/d, P < 0.001). The outcomes were alike in other respects. No subject had severe hypoglycemia.

CONCLUSIONS

Injection of 70/30 insulin before supper safely restored glycemic control of type 2 diabetes not controlled by glimepiride alone. Control was restored more rapidly and with less injected insulin when glimepiride was continued.
Postmenopausal Estrogens and Risk of Myocardial Infarction in Diabetic Women
Authors: Kaplan Robert C , Heckbert Susan R , Weiss Noel S , Wahl Patricia W , Smith Nicholas L , Newton Katherine M , Psaty Bruce M
Published: March 2007

OBJECTIVE

The effect of hormone replacement therapy on the risk of myocardial infarction in diabetic women has not been well studied. We conducted a case-control study of postmenopausal estrogen use and risk of incident myocardial infarction (MI) in pharmacologically treated diabetic women enrolled at Group Health Cooperative of Puget Sound, a large health maintenance organization in the state of Washington.

RESEARCH DESIGN AND METHODS

Case subjects (n = 212) were all postmenopausal women with treated diabetes who sustained an incident fatal or nonfatal MI between July 1986 and December 1994. Control subjects (n = 122) were treated diabetic women drawn from a stratified random sample of postmenopausal women without prior MI. Computerized pharmacy data and medical records were used to measure use of estrogens. Cardiovascular risk factors recorded from medical records, computerized pharmacy and laboratory data, and telephone interviews were used as adjustment variables.

RESULTS

In this study, 8.5% of case and 13.9% of control subjects were current users of estrogens. The relative risk (RR) of MI for current estrogen users was 0.51 (95% CI 0.22–1.15) relative to never users, adjusted for age, study year, weight, angina, and duration of treated diabetes. Among current estrogen users, risk of MI tended to decline with each additional year of estrogen use (adjusted RR – 0.78, 95% CI 0.56–1.08). Of those studied, 45.3% of case and 37.7% of control subjects were past users of estrogens (adjusted RR = 1.22,95% CI 0.71–2.09).

CONCLUSIONS

This study suggests that use of postmenopausal estrogens does not increase risk of MI in diabetic women and that sustained use may be of benefit.
Acarbose in NIDDM Patients With Poor Control on Conventional Oral Agents: A 24-week placebo-controlled study
Authors: Lam Karen SL , Tiu SC , Tsang MW , Ip TP , Tam Sidney CF
Published: March 2007

OBJECTIVE

To determine the efficacy of acarbose, compared with placebo, on the metabolic control of NIDDM patients inadequately controlled on maximal doses of conventional oral agents.

RESEARCH DESIGN AND METHODS

In this three-center double-blind study, 90 Chinese NIDDM patients with persistent poor glycemic control despite maximal doses of sulfonylurea and metformin were randomly assigned to receive additional treatment with acarbose 100 mg thrice daily or placebo for 24 weeks, after 6 weeks of dietary reinforcement. Efficacy was assessed by changes in HbA1c, fasting and 1-h postprandial plasma glucose and insulin levels, and fasting lipid levels.

RESULTS

Acarbose treatment was associated with significantly greater reductions in HbA1c (−0.5 ± 0.2% vs. placebo 0.1 ± 0.2% [means ± SEM], P = 0.038), 1-h postprandial glucose (−2.3 ± 0.4 mmol/1 vs. placebo 0.7 ± 0.4 mmol/1, P < 0.001) and body weight (−0.54 ± 0.32 kg vs. placebo 0.42 ± 0.29 kg, P < 0.05). There was no significant difference between the two groups regarding changes in fasting plasma glucose and lipids or fasting and postprandial insulin levels. Flatulence was the most common side effect (acarbose vs. placebo: 28/45 vs. 11/44, P < 0.05). One patient on acarbose had asymptomatic elevations in serum transaminases that normalized in 4 weeks after acarbose withdrawal. Another patient on acarbose developed severe hypoglycemia; glycemic control was subsequently maintained on half the baseline dosage of sulfonylurea.

CONCLUSIONS

In NIDDM patients inadequately controlled on conventional oral agents, acarbose in moderate doses resulted in beneficial effects on glycemic control, especially postprandial glycemia, and mean body weight. Additional use of acarbose can be considered as a useful alternative in such patients if they are reluctant to accept insulin therapy.