bluuebunny/crossref_metadata_2025 huggingface dataset:
Perinatal and neonatal determinants of childhood type 1 diabetes. A case-control study in Yorkshire, U.K.
Authors: McKinney P A , Parslow R , Gurney K A , Law G R , Bodansky H J , Williams R
Published: March 2007

OBJECTIVE: To identify environmental factors that exert their effect in the perinatal and neonatal period and influence the subsequent onset of insulin dependent (type 1) diabetes during childhood. RESEARCH DESIGN AND METHODS: A population-based case-control study of data abstracted from the hospital obstetric and neonatal records of 196 children with type 1 diabetes and 325 age- and sex-matched control subjects. Analysis of matched sets by conditional logistic regression was conducted for a range of perinatal and neonatal factors. RESULTS: A significantly raised risk was observed for illnesses in the neonatal period (OR 1.61, 95% CI 1.06-2.44), the majority of which were infections and respiratory difficulties. Exclusive breast feeding as the initial feeding method was significantly protective (OR 0.65, 95% CI 0.45-0.94). There were no significant associations with high- or low-birth weight, being firstborn or small-for-dates. All factors significant (5% level) for the entire dataset, that is, maternal age, type 1 diabetes in mothers, preeclampsia, delivery by cesarean section, neonatal illnesses, and initial breast feeding were modeled and the OR remained significant for all variables other than cesarean section. CONCLUSIONS: The findings are based on medical record data that cannot be subject to biased recall of mothers. Neonatal illnesses increased and initial breast feeding decreased the risk of childhood type 1 diabetes. Further determinants of risk are mothers with type 1 diabetes, older mothers, and preeclampsia during pregnancy.
Is pregnancy in diabetic women associated with folate deficiency?
Authors: Kaplan J S , Iqbal S , England B G , Zawacki C M , Herman W H
Published: March 2007

OBJECTIVE: To determine whether folate metabolism in pregnant diabetic women is significantly different from that in pregnant nondiabetic women, thus predisposing them to having offspring with major congenital anomalies. RESEARCH DESIGN AND METHODS: A total of 31 pregnant diabetic women and 54 pregnant nondiabetic control subjects were studied at their first prenatal visits. Dietary folate intake, serum folate, red blood cell folate, urinary folate, and homocysteine were measured and compared after controlling for folate supplementation. Among diabetic women the relationships among parameters of folate metabolism and glycemic control were also assessed. RESULTS: There were no significant differences between the pregnant diabetic and non-diabetic women for any measures of folate metabolism after accounting for folate supplementation. In addition, among diabetic women, there were no associations among parameters of folate metabolism and glycemic control. CONCLUSIONS: Abnormal folate metabolism does not appear to occur in pregnant diabetic women. It is unlikely that deranged folate metabolism explains the higher incidence of major anomalies in infants of diabetic mothers. These results do not diminish the importance of periconception folate supplementation or preclude other possible scenarios that could restrict folate use by the embryo, leading to congenital anomalies.
Blood glucose awareness training and epinephrine responses to hypoglycemia during intensive treatment in type 1 diabetes.
Authors: Kinsley B T , Weinger K , Bajaj M , Levy C J , Simonson D C , Quigley M , Cox D J , Jacobson A M
Published: March 2007

OBJECTIVE: To determine the effect of blood glucose awareness training (BGAT) on epinephrine and symptom responses to hypoglycemia in patients with type 1 diabetes enrolled in an intensive diabetes treatment (IDT) program. RESEARCH DESIGN AND METHODS: A total of 47 subjects with uncomplicated diabetes (duration 9 +/- 3 years: HbA1c 9.0 +/- 1.2%; reference range 4-6%) enrolled in a 4-month outpatient IDT program were randomized to classes in BGAT (n = 25) (BGAT group) or cholesterol awareness (n = 22) (control group). Subjects underwent stepped hypoglycemic clamp studies before and at completion of IDT. Plasma glucose was lowered from 6.7 mmol/l (baseline) to 4.4, 3.9, 3.3, 2.8, and 2.2 mmol/l over 190 min. Symptoms, counterregulatory hormones, and ability of the subject to estimate their glucose level were assessed at each plateau. At home, subjects used a handheld computer to first estimate and then measure and record blood glucose levels for 70 trials over a 4-week period immediately before IDT and again immediately following the educational intervention. RESULTS: HbA1c decreased in both BGAT group (9.1 +/- 1.4 to 7.9 +/- 1.1%; P < 0.001) and control group (9.0 +/- 1.1 to 7.8 +/- 0.8%; P < 0.001) (NS between groups). Frequency of hypoglycemia (< 3.9 mmol/l) increased in both groups, from 0.45 +/- 0.06 to 0.69 +/- 0.07 episodes per day (P < 0.001) in the BGAT group and from 0.50 +/- 0.08 to 0.68 +/- 0.06 episodes per day (P < 0.05) in the control group NS between groups). Epinephrine responses after IDT were greater in the BGAT group (repeated measure analysis of variance [ANOVA], F = 3.5, P < 0.05). A separate analysis of subjects n = 26) most at risk for hypoglycemia (HbA1c after IDT < 7.8% or an HbA1c improvement of > 2 percentage points) showed that frequency of hypoglycemia increased in both the groups: from 0.50 +/- 0.09 to 0.80 +/- 0.11 episodes per day (P < 0.01) in the BGAT group (n = 14) and from 0.43 +/- 0.11 to 0.75 +/- 0.07 episodes per day (P < 0.05) in the control group (n = 12) (NS between groups). However, the epinephrine response in control subjects decreased with IDT while the response in the BGAT subjects was preserved (repeated measure ANOVA, F = 4.4, P < 0.02). CONCLUSIONS: BGAT is a useful intervention to decrease blunting of counterregulatory responses associated with improved glycemic control and may modify the severity of hypoglycemia associated with improved glycemic control in type 1 diabetes.
Previous maternal abortion, longer gestation, and younger maternal age decrease the risk of type 1 diabetes among male offspring.
Authors: Bache I , Bock T , Vølund A , Buschard K
Published: March 2007

OBJECTIVE: To identify possible influences and interactions of perinatal determinants in the subsequent development of type 1 diabetes. RESEARCH DESIGN AND METHODS: The data were obtained from children born in Denmark during the periods 1978-1982 and 1984-1986 and admitted to a Danish hospital with newly diagnosed type 1 diabetes between 1978 and 1995; 857 patients fulfilled the criteria. The study was conducted by combining and analyzing two national registries: the National Patient Registry and the Medical Birth Registry. For each diabetic child, two control children were randomly selected, matched by sex, time, and district of delivery. RESULTS: By multivariate logistic regression analysis, the following significant determinants were identified. Male offspring showed decreased risk when born of mothers who had had one or more abortions (odds ratio [OR] 0.66 [95% CI 0.48-0.92]) and with long duration of gestation (linearly with OR 0.91 per week [0.85-0.99]), while increased risk was found for high maternal age (linearly with OR 1.03 per year [1.00-1.06]). Female offspring showed no such association. No significant differences between diabetic patients and control subjects were found with respect to paternal age, maternal parity, placental weight or any of the birth size parameters, or interventions and complications during delivery. CONCLUSIONS: The findings show that perinatal determinants may influence the risk of subsequent development of type 1 diabetes in a sex-specific manner.
The onset age of type 1 diabetes in Finnish children has become younger. The Finnish Childhood Diabetes Registry Group.
Authors: Karvonen M , Pitkäniemi J , Tuomilehto J
Published: March 2007

OBJECTIVE: To analyze the change in the age distribution at onset of type 1 diabetes in boys and girls aged 1-14 years during a 32-year period (from 1965 to 1996). RESEARCH DESIGN AND METHODS: Data on the incidence of type 1 diabetes in Finland were obtained from the Central Drug Registry of the Social Insurance Institution for 1965-1986 (6,195 cases) and from the Prospective Childhood Diabetes Registry for 1987-1996 (3,613 cases). The change in age- and sex-specific incidence was estimated by fitting the linear regression with the logarithm of the annual incidence data. Analysis of variance was used to compare the trends between the various age-groups (1-4, 5-9, and 10-14 years) and sexes. RESULTS: The incidence of type 1 diabetes increased predominantly in the younger age-groups. In children aged 1-4 years, the increase was 4.2% per year, and the overall 32-year relative increase was 338%. For children aged 5-9 and 10-14 years, the increase was 2.5 and 1.3% per year, respectively, and the overall relative increase was 116 and 49%, respectively. In boys aged 1-9 years, the increase was greatest from 1965 to 1984, whereas in girls aged 1-9 years, the statistically significant increase occurred between 1985 and 1996. In children aged 10-14 years, the only significant increase was seen in boys from 1965 to 1974 (3.7% per year). CONCLUSIONS: The greatest increase in the incidence of type 1 diabetes mainly occurred in children aged < 5 years. The incidence in young boys has been increasing since the mid-1960s, whereas in young girls, the significant increase began later, around the mid-1970s. In children aged 10-14 years, the increase in incidence has leveled off.
Conventional versus intensive diabetes therapy in children with type 1 diabetes: effects on memory and motor speed.
Authors: Hershey T , Bhargava N , Sadler M , White N H , Craft S
Published: March 2007

OBJECTIVE: Severe hypoglycemia may impair medial temporal-mediated cognitive skills, such as the ability to recall past events explicitly (delayed declarative memory). The objective of this study was to determine whether delayed declarative memory deficits are present in a group of diabetic children with an increased risk of severe hypoglycemia. RESEARCH DESIGN AND METHODS: Nondiabetic children (n = 16) and children with type 1 diabetes who had been randomly assigned to either intensive (IT) (n = 13) or conventional (CT) (n = 12) diabetes therapy at the time of diagnosis participated in the study. All episodes of severe hypoglycemia were prospectively ascertained. All children were tested on memory tasks that have been closely linked to medial temporal functioning and on reaction time measures. RESULTS: Our results demonstrated that the IT group had a threefold higher rate of severe hypoglycemia, performed less accurately on a spatial declarative memory task, and performed more slowly, but not less accurately, on a pattern recognition task than did the CT group or control subjects. In addition, both groups of type 1 diabetic children were significantly impaired on a motor speed task compared with their nondiabetic peers. CONCLUSIONS: These results indicate a selective relative memory impairment associated with IT that is consistent with the effects of severe hypoglycemia and medial temporal damage or dysfunction. If larger prospective studies determine that severe hypoglycemia is the mediating factor for this memory impairment, extreme caution in imposing overly strict standards for glucose control in young patients with type 1 diabetes would be indicated because of the increased risk of hypoglycemia associated with IT regimens.
Plasma glucose within the normal range is not associated with carotid atherosclerosis: prospective results in subjects with normal glucose tolerance from the Bruneck Study.
Authors: Bonora E , Kiechl S , Willeit J , Oberhollenzer F , Egger G , Bonadonna R , Muggeo M
Published: March 2007

OBJECTIVE: There is substantial evidence that glucose intolerance is associated with an increased risk of cardiovascular disease. However, it is not well established whether plasma glucose is independently related to atherosclerosis when glucose tolerance is normal and, if so, to which stage of the complex atherosclerotic process. RESEARCH DESIGN AND METHODS: We prospectively examined the status of carotid arteries in 625 subjects aged 40-79 years who were randomly selected from the general population and had normal glucose tolerance (according to World Health Organization criteria) both at baseline and at 5 years of follow-up. All subjects had high-resolution echo-duplex evaluation of the common and internal carotid arteries (eight regions of interest on both sides) in 1990 and 1995 to detect the change in carotid status over time. The occurrence of new plaques in previously normal segments was termed "incident nonstenotic" or "early atherosclerosis," and the occurrence of stenosis in >40% of previously normal segments was termed "incident stenotic" or "advanced atherosclerosis." In addition, we evaluated the changes in the atherosclerosis score (the sum of all plaques) during the follow-up, and we measured intimal-medial thickening (IMT) in the common carotid artery in 1995. In all subjects, several candidate risk factors were assessed: sex, age, BMI, waist-to-hip ratio, glucose, HbA1c, insulin, urate, lipids, apolipoproteins A1 and B, blood pressure, lipoprotein(a), fibrinogen, antithrombin III, factor V Leiden mutation, ferritin, leukocyte count, smoking, alcohol intake, physical activity, and socioeconomic status. Fasting plasma glucose (FPG), plasma glucose 2 hr after the glucose load (2-h PG), and HbA1c concentrations in 1990 and 1995 were averaged in each subject to obtain an estimate of long-term glucose exposure of the arterial wall. RESULTS: Linear or logistical regression analyses indicated that neither baseline glucose and HbA1c levels nor mean FPG, mean 2-h PG, or mean HbA1c in 1990 and 1995 were independently related to IMT, a 5-year change in the atherosclerotic score, incident nonstenotic (early) atherosclerosis, or incident stenotic (advanced) atherosclerosis. Likewise, subjects with FPG levels above the median and subjects in the new category of "impaired fasting glucose" did not have an increased occurrence or progression of atherosclerosis. All results were consistent before and after adjustment for other vascular risk factors and possible confounders. CONCLUSIONS: These results suggest that plasma glucose levels within the normal range (<7.8 mg/dl both at FPG and 2-h PG) are not independently related to any stage of atherosclerosis.
Diabetes in urban African-Americans. XVI. Overcoming clinical inertia improves glycemic control in patients with type 2 diabetes.
Authors: Cook C B , Ziemer D C , El-Kebbi I M , Gallina D L , Dunbar V G , Ernst K L , Phillips L S
Published: March 2007

OBJECTIVE: Diabetes care can be limited by clinical inertia-failure of the provider to intensify therapy when glucose levels are high. Although disease management programs have been proposed as a means to improve diabetes care, there are few studies examining their effectiveness in patient populations that have traditionally been underserved. We examined the impact of our management program in the Grady Diabetes Unit, which provides care primarily to urban African-American patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We assessed glycemic outcomes in patients with type 2 diabetes who had an intake evaluation between 1992 and 1996 and who were identified on the basis of compliance with keeping the recommended number of return visits. For 698 patients, we analyzed changes in HbA1c values between baseline and follow-up visits at 6 and 12 months, and the proportion of patients achieving a target value of < or =7.0% at 12 months. Since a greater emphasis on therapeutic intensification began in 1995, we also compared HbA1c values and clinical management in 1995-1996 with that of 1992-1994. RESULTS: HbA1c averaged 9.3% on presentation. After 12 months of care, HbA1c values averaged 8.2, 8.4, 8.5, 7.7, and 7.3% for the 1992-1996 cohorts, respectively, and were significantly lower compared with values on presentation (P < 0.0025); the average fall in HbA1c was 1.4%. The percentage of patients achieving a target HbA1c < or =7.0% improved progressively from 1993 to 1996, with 57% of the patients attaining this goal in 1996. Mean HbA1c after 12 months was 7.6% in 1995-1996, significantly improved over the level of 8.4% in 1992-1994 (P < 0.0001). HbA1c levels after 12 months of care were lower in 1995-1996 versus 1992-1994, whether patients were managed with diet alone, oral agents, or insulin (P < 0.02). Improved HbA1c in 1995-1996 versus 1992-1994 was associated with increased use of pharmacologic therapy CONCLUSIONS: Structured programs can improve glycemic control in urban African-Americans with diabetes. Self-examination of performance focused on overcoming clinical inertia is essential to progressive upgrading of care.
Total homocysteine in patients with type 1 diabetes.
Authors: Pavía C , Ferrer I , Valls C , Artuch R , Colomé C , Vilaseca M A
Published: March 2007

OBJECTIVE: Our aim was to study the presence of moderate hyperhomocysteinemia, a risk factor for premature cardiovascular disease, its modifying vitamin factors (folates, vitamins B12 and B6), and lipid risk factors in juvenile type 1 diabetes. RESEARCH DESIGN AND METHODS: A total of 91 patients with type 1 diabetes (46 girls and 45 boys) were studied, with ages ranging from 11 to 18 years, a duration of diabetes from 1 to 15 years, and in pubertal development (stages III, IV, V). In all patients, cholesterol, triglycerides, HDL and LDL cholesterol, lipoprotein(a), folates, cobalamin, vitamin B6, and total homocysteine were determined by specific assays. Microalbuminuria, defined as a ratio of albumin/creatinine >3 mg/mmol creatinine, was analyzed in the first morning specimen. RESULTS: Plasma total homocysteine (tHcy) concentrations were not different in the 91 diabetic children (median [range]) (11-15 years, 6.1 micromol/l [3.2-9.6]; 16-18 years, 7.3 micromol/l [3.9-12]) compared with the control group (11-15 years, 6.6 micromol/l [4.4-10.8]; 16-18 years, 8.1 micromol/l [4.6-11.3]). No significant differences were found in tHcy values in relation to the metabolic control of the disease as assessed by glycohemoglobin values, the duration of disease, alterations in fundus oculi, or presence of lymphocytic thyroiditis. A positive correlation was found between tHcy and plasma creatinine in type 1 diabetic patients that might be related with the increase in muscle mass. There was a negative correlation between tHcy and serum folate (P<0.001) and vitamin B12 (P<0.05), but not with vitamin B6 levels. No significant correlations were found between tHcy and the lipid parameters. CONCLUSIONS: Hyperhomocysteinemia was not detected in adolescents with type 1 diabetes.
Effects of cyclo-oxygenase inhibition on vasodilatory response to acetylcholine in patients with type 1 diabetes and nondiabetic subjects.
Authors: Meeking D R , Browne D L , Allard S , Munday J , Chowienczyck P J , Shaw K M , Cummings M H
Published: March 2007

OBJECTIVE: Studies examining vasodilatory responses to acetylcholine (ACh) and its derivatives have been conflicting. Enhanced activation of the cyclo-oxygenase pathway and increased availability of vasodilatory prostanoids may occur in type 1 diabetes, and this may compensate for the observed reduction in nitric oxide (NO) activity We examined the role of cyclo-oxygenase inhibition on vasodilatory responses in 12 healthy normotensive type 1 diabetic adults and 12 nondiabetic control subjects of similar age, sex, and BMI. RESEARCH DESIGN AND METHODS: Forearm blood flow was measured using a venous occlusion plethysmography technique at baseline and after brachial artery infusions of ACh (7.5, 15, and 30 microg/min). Forearm blood flow at baseline and after ACh was then reexamined after local intra-arterial infusion of indomethacin (0.3 mg/100 ml forearm volume), a cyclo-oxygenase inhibitor. RESULTS: Baseline blood flow in the diabetic and control groups were similar (2.65 +/- 0.26 vs. 2.59 +/- 0.20 ml/min per 100 ml, respectively; P = 0.4). After indomethacin infusion, the vasodilatory responses to all doses of ACh were reduced in both the diabetic (by 25.30 +/- 4.90%) and control group (by 11.23 +/- 5.45%). However, the reduction in blood flow response to ACh after indomethacin was greater in diabetic patients compared with control subjects (P = 0.03). CONCLUSIONS: Our findings suggest that vasodilatory, prostanoids are important in determining endothelial response to ACh in diabetic and nondiabetic subjects. Increased prostaglandin-mediated vasodilation may compensate for attenuated responses to NO previously reported in diabetic subjects. These findings may partly explain the conflicting reports of endothelial dysfunction in patients with type 1 diabetes.
Moderate-intensity physical activity and fasting insulin levels in women: the Cross-Cultural Activity Participation Study.
Authors: Irwin M L , Mayer-Davis E J , Addy C L , Pate R R , Durstine J L , Stolarczyk L M , Ainsworth B E
Published: March 2007

OBJECTIVE: The purpose of this study was to determine the association between moderate-intensity physical activity (PA) and fasting insulin levels among African-American (n = 47), Native American (n = 46), and Caucasian women (n = 49), aged 40-83 years, enrolled in the Cross-Cultural Activity Participation Study. Associations by race/ethnicity, levels of central obesity, and cardiorespiratory fitness were also examined. RESEARCH DESIGN AND METHODS: Physical activity scores were obtained from detailed PA records that included all PA performed during two consecutive 4-day periods scheduled 1 month apart. Using MET intensity (the associated metabolic rate for a specific activity divided by a standard resting metabolic rate), PA was expressed as MET-min (the product of the minutes for each activity times the MET intensity level) per day of energy expended in moderate (3-6 METs) and moderate/vigorous (> or = 3 METs) PA. Fasting insulin levels were determined by radioimmunoassay. Data were analyzed by multiple linear regression analysis. RESULTS: After adjusting for race/ethnicity, age, educational attainment, and site, an increase of 30 min of moderate-intensity PA was associated with a 6.6% lower fasting insulin level (P < 0.05). The association was similar among races/ethnicities, centrally lean and centrally obese women, and women with low and high cardiorespiratory fitness levels. CONCLUSIONS: These findings lend support to the 1995 Centers for Disease Control and Prevention and American College of Sports Medicine recommendations for an accumulation of 30 min/day in moderate-intensity PA. They also contribute to the growing literature suggesting that moderate amounts of PA have a significant role in reducing the burden of hyperinsulinemia and diabetes among ethnic populations at highest risk for these conditions.
Patterns of quantitative sensation testing of hypoesthesia and hyperalgesia are predictive of diabetic polyneuropathy: a study of three cohorts. Nerve growth factor study group.
Authors: Dyck P J , Dyck P J , Larson T S , O'Brien P C , Velosa J A
Published: March 2007

OBJECTIVE: To test quantitative sensation testing (QST) patterns of hypoesthesia and hyperalgesia as indicators of diabetic polyneuropathy (DPN) and its severity RESEARCH DESIGN AND METHODS: We used Computer-Assisted Sensory Examination IV; characterized the QST results of the foot of each patient in three diabetic cohorts (approximately 1,500 patients) as hyperesthetic (< or = 2.5th percentile), low-normal (2.5th-50th percentiles), high-normal (50th-97.5th percentiles), or hypoesthetic (> or = 97.5th percentile); and tested associations with symptoms, impairments, and test abnormalities. RESULTS: Overall neuropathic impairment was most severe in the pancreas-renal transplant and nerve growth factor cohorts, but it was much less severe in the population-based Rochester Diabetic Neuropathy Study (RDNS) cohort. The frequency distribution of sensory abnormalities mirrored this difference. When the QST spectra of diabetic cohorts were compared with those of the control subject cohort for vibration and cooling sensations, the only abnormality observed was hypoesthesia, which was expressed as an increased number of subjects with values at or above the 97.5th percentile or by an increased percentage of cases with high-normal values. Symptoms and impairments of DPN were significantly more frequent in the subjects with values at or above the 97.5th percentile than in the subjects whose values were between the 50th and 97.5th percentiles. For heat pain (HP) sensation thresholds (intermediate pain severity [HP:5], pain threshold [HP:0.5], and pain-stimulus response slope [HP:5-0.5]), an increased frequency of both hypoalgesia and hyperalgesia was observed (especially in the RDNS cohort). Steeper pain-stimulus response slopes were significantly associated with sensory symptoms, including severity of pain. CONCLUSIONS: 1) Decreased vibratory sensation (hypoesthesia) appears to be characteristic of mild DPN, whereas panmodality hypoesthesia is characteristic of severe DPN. 2) A shift of vibratory and cold detection thresholds (and also of attributes of nerve conduction and a measure of autonomic dysfunction) from low-normal (2.5th-50th percentiles) to high-normal (50th-97.5th percentiles) appears to precede overt expression of DPN and to thereby provide evidence of subclinical abnormality 3) Heat stimulus-induced hyperesthesia (low thresholds) occurs especially in mild DPN, and, because it correlates with DPN symptoms and impairments, it must be attributed to hyperalgesia rather than to supersensitivity Therefore, hypoalgesia or hyperalgesia may be an indicator of early DPN.
Cigarette smoking and plasma total homocysteine levels in young adults with type 1 diabetes.
Authors: Targher G , Bertolini L , Zenari L , Cacciatori V , Muggeo M , Faccini G , Zoppini G
Published: March 2007

OBJECTIVE: The purposes of this study were to compare plasma total homocysteine (tHcy) levels, a recognized cardiovascular risk factor, in nondiabetic subjects and type 1 diabetic patients, and to evaluate whether chronic cigarette smoking had a deleterious effect on plasma tHcy levels in type 1 diabetic patients. RESEARCH DESIGN AND METHODS: Plasma tHcy concentrations were measured in 60 young type 1 diabetic patients without clinical evidence of macroangiopathy and in 30 healthy control subjects who were matched for age, sex, BMI, and smoking habit. RESULTS: Plasma tHcy levels were significantly higher in type 1 diabetic patients than in control subjects (12.5 +/- 4.8 vs. 10.3 +/- 2.2 micromol/l, P = 0.01). After stratification by smoking status, diabetic smokers had values for age, sex, BMI, lipids, creatinine, blood pressure, glycometabolic control, diabetes duration, and microvascular complications that were superimposable on their nonsmoking counterparts. Nevertheless, plasma tHcy levels were markedly elevated in diabetic smokers versus nonsmokers (15.5 +/- 5.7 vs. 10.6 +/- 3 pmol/l, P < 0.0001) in a dose-dependent fashion (P < 0.0001, by analysis of variance when subjects were categorized for the number of cigarettes smoked daily). CONCLUSIONS: Chronic cigarette smoking seems to adversely affect plasma tHcy levels in young adults with type 1 diabetes.
Assessing impaired hypoglycemia awareness in type 1 diabetes: agreement of self-report but not of field study data with the autonomic symptom threshold during experimental hypoglycemia.
Authors: Janssen M M , Snoek F J , Heine R J
Published: March 2007

OBJECTIVE: The aim of our study was to determine the agreement of two noninvasive methods, a self-report and a field study method, for the assessment of impaired hypoglycemia awareness with a gold standard criterion of hypoglycemia awareness, the autonomic symptom threshold during experimental hypoglycemia. RESEARCH DESIGN AND METHODS: A total of 19 type 1 diabetic patients completed a standardized questionnaire to assess impaired hypoglycemia awareness and performed a hand-held computer (HHC) study to assess their recognition of hypoglycemic episodes occurring during 24 weeks. Patients subsequently underwent a stepped hypoglycemic clamp to study responses to standardized hypoglycemia. Diagnoses of impaired hypoglycemia awareness were based on the separate self-report questions, a composite self-report score, and three different cutoff levels for the percentage of accurately recognized hypoglycemic episodes during the field study Agreement of these noninvasive measures with the hypoglycemic clamp measure were tested by calculating kappa values, sensitivity, and specificity. RESULTS: The composite self-report score agreed reasonably well with the hypoglycemic clamp measure (kappa 0.49, sensitivity 66.7%, and specificity 85.7%) and showed a better agreement than the separate self-report questions. The HHC criterion of impaired hypoglycemia awareness did not agree with the hypoglycemic clamp criterion at any of the cutoff levels tested. CONCLUSIONS: The composite self-report tested in this study is a reasonably reliable assessment method for the diagnosis of impaired hypoglycemia awareness, using the physiological definition of an absence of autonomic symptoms at a blood glucose level of 3 mmol/l. In contrast, the recognition of hypoglycemic events in everyday life as measured using the HHC method is not related to the hypoglycemic clamp criterion.
Sex differentials in predictors of mortality for patients with adult-onset diabetes: a population-based follow-up study in Beer-Sheva, Israel.
Authors: Biderman A , Rosenblatt I , Rosen S , Zangwill L M , Shalev R , Friger M , Weitzman S
Published: March 2007

OBJECTIVE: To test the hypothesis that factors predicting mortality differ between diabetic men and women. RESEARCH DESIGN AND METHODS: A total of 498 known patients with diabetes residing in a well-defined geographical area and receiving primary health care in 3 primary care community clinics were interviewed and examined between 1988 and 1990. RESULTS: By 31 July 1998, after a mean follow-up period of 7.8 years, 148 patients (68 men and 80 women) had died (29.7%). No statistical differences in survival rate or in the specific causes of death were found between men and women. In the univariate analysis of factors examined at baseline, GHb levels were significantly higher among women who died compared with women who survived, but this was not the case for men. Conversely, a trend of higher triglyceride and uric acid levels was found for men who died compared with men who survived, but this was not the case for women. Multivariate Poisson regression analysis showed significantly higher risk ratios for mortality in men > or = 63 years of age, men with microalbumin excretion > or = 30 mg/l, and men with higher triglyceride levels. In contrast, the analysis in women showed that higher GHb and creatinine levels and a reported history of heart disease were the only factors at the baseline examination significantly and independently associated with an increased risk ratio of mortality. CONCLUSIONS: The results suggest the existence of sex-specific interactions with various metabolic factors associated with diabetes that may have a different effect on mortality for each sex.
Vitamin C and hyperglycemia in the European Prospective Investigation into Cancer--Norfolk (EPIC-Norfolk) study: a population-based study.
Authors: Sargeant L A , Wareham N J , Bingham S , Day N E , Luben R N , Oakes S , Welch A , Khaw K T
Published: March 2007

OBJECTIVE: To examine the cross-sectional association between plasma vitamin C, self-reported diabetes, and HbA1c. RESEARCH DESIGN AND METHODS: Data from a population-based study of diet, cancer, and chronic disease were analyzed. A total of 2,898 men and 3,560 women 45-74 years of age who were registered with general practices in Norfolk, U.K., were recruited to the European Prospective Investigation Into Cancer-Norfolk study between 1995 and 1998. RESULTS: Mean plasma vitamin C levels were significantly higher in individuals with HbA1c levels < 7% than in those with self-reported diabetes or prevalent undiagnosed hyperglycemia (HbA1c > or = 7%). An inverse gradient of mean plasma vitamin C was found in both sexes across quintiles of HbA1c distribution < 7%. The odds ratio (95% CI) of having prevalent undiagnosed hyperglycemia per 20 micromol/l (or 1 SD) increase in plasma vitamin C was 0.70 (0.52-0.95) (adjusted for sex, age, BMI, waist-to-hip ratio, tertiary education, any use of dietary supplements, vegetarian diet, alcohol consumption, physical activity, dietary vitamin E, dietary fiber, dietary saturated fat, and smoking history). The unadjusted change in HbA1c per 20 micromol/l increase in vitamin C estimated by linear regression was -0.12% (-0.14 to -0.09) in men and -0.09% (-0.11 to -0.07) in women. After adjusting for the possible confounders, these values were -0.08% (-0.11 to -0.04) in men and -0.05% (-0.07 to -0.03) in women. CONCLUSIONS: An inverse association was found between plasma vitamin C and HbA1c. Dietary measures to increase plasma vitamin C may be an important public health strategy for reducing the prevalence of diabetes.
Impact of type 1 and type 2 diabetes on patterns and costs of drug prescribing: a population-based study.
Authors: Evans J M , MacDonald T M , Leese G P , Ruta D A , Morris A D
Published: March 2007

OBJECTIVE: Utilization and costs of prescription drugs were investigated in diabetic and nondiabetic patients. RESEARCH DESIGN AND METHODS: The study was carried out in Tayside, Scotland, U.K. A validated population-based diabetes register was used to identify patients with type 1 and type 2 diabetes, and a database of all prescriptions dispensed in the community was used to investigate drug utilization in 1995. RESULTS: In a population of 406,526, there were 974 (0.2%) with type 1 diabetes and 6,869 (1.7%) with type 2 diabetes. The mean dispensed prescribing rates for all drugs (excluding antidiabetic medication) were higher across all age-groups for diabetic patients. After adjusting for age, patients with type 1 diabetes were 2.07 times (95% CI 2.03-2.11) more likely and patients with type 2 diabetes were 1.70 times (1.69-1.71) more likely to be dispensed a drug item than people without diabetes. This likelihood was increased in every drug category, even those not directly related to diabetes, and the proportion and cost of drug items dispensed to diabetic patients was therefore higher than expected given the prevalence of diabetes. Upon projecting these results to the U.K. population, it was discovered that nearly 8% of the U.K. drug budget (Pound Sterling 350 million) is accounted for by patients with diabetes (90% of that by patients with type 2 diabetes). CONCLUSIONS: This study highlights the increased usage and cost of prescription drugs in diabetes, with type 2 diabetes constituting a particular burden. It was discovered that 1.4% of drug usage in the entire population can be accounted for by the increased prescribing rate of diabetic patients compared with that of nondiabetic patients.
Clinical utility of HNF1A genotyping for diabetes in aboriginal Canadians.
Authors: Hegele R A , Cao H , Hanley A J , Zinman B , Harris S B , Anderson C M
Published: March 2007

OBJECTIVE: To determine the diagnostic performance characteristics of HNF1A genotyping for diabetes and impaired glucose tolerance (IGT) in Canadian Oji-Cree Indians. RESEARCH DESIGN AND METHODS: We studied all Oji-Cree subjects > or = 50 years of age (96 subjects) who had participated in a community-wide prevalence survey for type 2 diabetes. Subjects were classified either as having "disease," which included type 2 diabetes and IGT, or not. All subjects were genotyped for the HNF1A G319S mutation. RESULTS: The prevalence of disease in this group was 65.7%, of whom 71.4% had type 2 diabetes. For a carrier of HNF1A S319, the specificity, sensitivity, and positive and negative predictive values were 97.0, 30.1, 95.0, and 42.1%, respectively. When the pretest disease prevalence was accounted for, the probability of disease after a positive test was 97.2%, and the probability of disease after a negative test was 42.2%. The values were very similar for the subgroup of subjects with type 2 diabetes alone. CONCLUSIONS: The HNF1A genotype appears to be the most specific genetic test yet reported for the prediction of a common multifactorial disease by applying present-day standards of clinical epidemiology in molecular genetics. A positive test result had particular diagnostic value in the Oji-Cree: a subject with HNF1A S319 was virtually certain of having diabetes or IGT by 50 years of age. In contrast, a subject without HNF1A S319 had a reduced risk compared with the age-specific prevalence but was not totally risk-free. Because HNF1A S319 was not the only predisposing factor for diabetes in the Oji-Cree, subjects without HNF1A S319 were still at some risk for diabetes or IGT.
Evaluation of beta-cell secretory capacity using glucagon-like peptide 1.
Authors: Vilsbøll T , Toft-Nielsen M B , Krarup T , Madsbad S , Dinesen B , Holst J J
Published: March 2007

OBJECTIVE: Beta-cell secretory capacity is often evaluated with a glucagon test or a meal test. However, glucagon-like peptide 1 (GLP-1) is the most insulinotropic hormone known, and the effect is preserved in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: We first compared the effects of intravenous bolus injections of 2.5, 5, 15, and 25 nmol GLP-1 with glucagon (1 mg intravenous) and a standard meal (566 kcal) in 6 type 2 diabetic patients and 6 matched control subjects. Next, we studied another 6 patients and 6 control subjects and, in addition to the above procedure, performed a combined glucose plus GLP-1 stimulation, where plasma glucose was increased to 15 mmol/l before injection of 2.5 nmol GLP-1. Finally, we compared the insulin response to glucose plus GLP-1 stimulation with that observed during a hyperglycemic arginine clamp (30 mmol/l) in 8 patients and 8 control subjects. RESULTS: Peak insulin and C-peptide concentrations were similar after the meal, after 2.5 nmol GLP-1, and after glucagon. Side effects were less with GLP-1 than with glucagon. Peak insulin and C-peptide concentrations were as follows (C-peptide concentrations are given in parentheses): for patients (n = 12): meal, 277 +/- 42 pmol/l (2,181 +/- 261 pmol/l); GLP-1 (2.5 nmol), 390 +/- 74 pmol/l (2,144 +/- 254 pmol/l); glucagon, 329 +/- 50 pmol/l (1,780 +/- 160 pmol/l); glucose plus GLP-1, 465 +/- 87 pmol/l (2,384 +/- 299 pmol/l); for control subjects (n = 12): meal, 543 +/- 89 pmol/l (2,873 +/- 210 pmol/l); GLP-1, 356 +/- 51 pmol/l (2,001 +/- 130 pmol/l); glucagon, 420 +/- 61 pmol/l (1,995 +/- 99 pmol/l); glucose plus GLP-1, 1,412 +/- 187 pmol/l (4,391 +/- 416 pmol/l). Peak insulin and C-peptide concentrations during the hyperglycemic arginine clamp and during glucose plus GLP-1 injection were as follows: for patients: 475 +/- 141 pmol/l (2,295 +/- 379 pmol/l) and 816 +/- 268 pmol/l (3,043 +/- 508 pmol/l), respectively; for control subjects: 1,403 +/- 308 pmol/l (4,053 +/- 533 pmol/l) and 2,384 +/- 452 pmol/l (6,047 +/- 652 pmol/l), respectively. CONCLUSIONS: GLP-1 (2.5 nmol = 9 microg) elicits similar secretory responses to 1 mg glucagon (but has fewer side effects) and a standard meal. Additional elevation of plasma glucose to 15 mmol/l did not enhance the response further. The incremental response was similar to that elicited by arginine, but hyperglycemia had an additional effect on the response to arginine.
Therapeutic benefits of ACE inhibitors and other antihypertensive drugs in patients with type 2 diabetes.
Authors: Pahor M , Psaty B M , Alderman M H , Applegate W B , Williamson J D , Furberg C D
Published: March 2007

OBJECTIVE: To assess whether ACE inhibitors are superior to alternative agents for the prevention of cardiovascular events in patients with hypertension and type 2 diabetes. RESEARCH DESIGN AND METHODS: This study is a review and meta-analysis of randomized controlled trials that included patients with type 2 diabetes and hypertension who were randomized to an ACE inhibitor or an alternative drug, were followed for > or =2 years, and had adjudicated cardiovascular events. RESULTS: A total of 4 trials were eligible. The Appropriate Blood Pressure Control in Diabetes (ABCD) trial (n = 470) compared enalapril with nisoldipine, the Captopril Prevention Project (CAPPP) (n = 572) compared captopril with diuretics or beta-blockers, the Fosinopril Versus Amlodipine Cardiovascular Events Trial (FACET) (n = 380) compared fosinopril with amlodipine, and the U.K. Prospective Diabetes Study (UKPDS) (n = 758) compared captopril with atenolol. The cumulative results of the first 3 trials showed a significant benefit of ACE inhibitors compared with alternative treatments on the outcomes of acute myocardial infarction (63% reduction, P < 0.001), cardiovascular events (51% reduction, P < 0.001), and all-cause mortality (62% reduction, P = 0.010). These findings were not observed in the UKPDS. The ACE inhibitors did not appear to be superior to other agents for the outcome of stroke in any of the trials. None of the findings were explained by differences in blood pressure control. CONCLUSIONS: Compared with the alternative agents tested, ACE inhibitors may provide a special advantage in addition to blood pressure control. The question of whether atenolol is equivalent to captopril remains open. Conclusive evidence on the comparative effects of antihypertensive treatments will come from large prospective randomized trials.
Reduced prevalence of impaired glucose tolerance and no change in prevalence of diabetes despite increasing BMI among Aboriginal people from a group of remote homeland communities.
Authors: Rowley K G , Gault A , McDermott R , Knight S , McLeay T , O'Dea K
Published: March 2007

OBJECTIVE: To examine trends in glucose tolerance and coronary risk among Aboriginal people from a group of homeland communities in central Australia during a 7-year follow-up period. RESEARCH DESIGN AND METHODS: Community-based screenings of adult volunteers were performed in 1988 (n = 437; 93% response rate) and in 1995 (n = 424; 85% response rate). A health promotion intervention program commenced after the 1988 survey that focused on the benefits of exercise and appropriate diet. RESULTS: Mean (95% CI) BMI increased significantly from 22.8 kg/m2 (22.3-23.2) to 24.2 kg/m2 (23.8-24.7) during the follow-up period (P < 0.001). This increase was similar for men and women and across all age-groups. The increase in BMI was greater among subjects residing adjacent to a store compared with those residing in communities located far from a store (P < 0.001). Decreases were evident in the prevalence of impaired glucose tolerance (IGT) (from 22.5 to 10.1% among women, P < 0.001; from 12.2 to 6.5% among men, P = 0.074) and hypercholesterolemia (from 36.7 to 25.8% among women, P < 0.01; from 52.4 to 44.0% among men, P = 0.147), but no change was evident in the prevalence of diabetes. Smoking remained rare among women (<4%) and decreased among men (from 52.9 to 40.8%, P < 0.05). CONCLUSIONS: The trends in glucose intolerance were clearly better than have been observed in other Aboriginal communities. The institution of an intervention program corresponded with reductions in the prevalence of IGT, hypercholesterolemia, and smoking. The prevalence of diabetes remained unaltered despite a significant increase in mean BMI, possibly because of the promotion of increased physical activity levels.
Association of CTLA-4 gene A/G polymorphism in Japanese type 1 diabetic patients with younger age of onset and autoimmune thyroid disease.
Authors: Takara M , Komiya I , Kinjo Y , Tomoyose T , Yamashiro S , Akamine H , Masuda M , Takasu N
Published: March 2007

OBJECTIVE: We studied the association between type 1 diabetes with autoimmune thyroid disease (AITD) and A/G allele polymorphism in exon 1 of the CTLA-4 gene in a Japanese population. RESEARCH DESIGN AND METHODS: We studied 74 Japanese type 1 diabetic patients with or without AITD and 107 normal subjects to identify the association between CTLA-4 polymorphism and type 1 diabetes using polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: The frequency of the CTLA-4 G allele differed significantly between the type 1 diabetic patients (61%) and the normal control subjects (48%) (P = 0.016). The difference in the CTLA-4 G allele became greater between patients with a younger age of onset of type 1 diabetes (age at onset <30 years) and the normal control subjects (64% and 48%, respectively). However, the frequency of the CTLA-4 G allele did not differ between type 1 diabetic patients with younger and older age of onset (64% vs. 57%). The G allele frequencies in the patients with younger-onset type 1 diabetes and AITD increased more than in the control patients (P = 0.025). These differences reflected a significant increase in the frequency of G/G genotype--that is, 54% in those with younger-onset type 1 diabetes and AITD, 39% in those without AITD, and 28% in control subjects. CONCLUSIONS: An association was detected between the CTLA-4 gene polymorphism and younger-onset type 1 diabetes with AITD. The G variant was suggested to be genetically linked to AITD-associated type 1 diabetes of younger onset in this apanese population. The defect in these patients presumably lies in a T-cell-mediated autoimmune mechanism.
Use of an islet cell antibody assay to identify type 1 diabetic patients with rapid decrease in C-peptide levels after clinical onset. Belgian Diabetes Registry.
Authors: Decochez K , Keymeulen B , Somers G , Dorchy H , De Leeuw I H , Mathieu C , Rottiers R , Winnock F , ver Elst K , Weets I , Kaufman L , Pipeleers D G , Rottiers R ,   Belgian Diabetes Registry
Published: March 2007

OBJECTIVE: To investigate whether the presence of antibody markers at diagnosis could help predict the rapid decrease in residual beta-cell function noted in some, but not all, patients with recent-onset type 1 diabetes. RESEARCH DESIGN AND METHODS: We measured random C-peptide levels (radioimmunoassay); islet cell cytoplasmic antibodies (ICA) (indirect immunofluorescence); and antibodies against IA-2 protein, 65-kDa glutamate decarboxylase, and insulin (liquid-phase radiobinding assays) in 172 patients <40 years of age with type 1 diabetes. The patients had been consecutively recruited at diagnosis by the Belgian Diabetes Registry and were followed for 2 years. RESULTS: Two years after diagnosis, random C-peptide levels had decreased significantly (P < 0.001) in ICA+ patients but not in ICA- patients. C-peptide values <50 pmol/ were noted in 88% of patients diagnosed before 7 years of age, in 45% of patients diagnosed between ages 7 and 15 years, and in 29% of patients diagnosed after 15 years of age (P < 0.001). In cases of clinical onset before age 15 years, a rapid decline in random C-peptide values was observed almost exclusively in patients with high-titer ICA (> or =50 Juvenile Diabetes Foundation [JDF] units) at diagnosis (69 vs. 17% in patients with lower ICA titers, P < 0.001). In patients diagnosed after 15 years of age, 36% of patients with ICA titers > or =12JDF units developed low C-peptide levels compared with 14% of patients with ICA titers < 12 JDF units (P < 0.03). Multivariate analysis confirmed that C-peptide levels after 2 years were inversely correlated with ICA levels (P < 0.001) and to a lesser degree positively correlated with age at diagnosis (P < 0.02), regardless of the levels or number of molecular autoantibodies. CONCLUSIONS: Young age at diagnosis and high-titer ICA identify a group of type 1 diabetic patients at high risk of rapidly losing residual beta-cell function. Using these selection criteria, it is possible to better target beta-cell-preserving interventions to patients with or without such rapid progression, depending on the nature of the tested substance. The ICA assay measures clinically relevant antibodies not detected in antibody assays that use recombinant human autoantigens for substrate.