bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of repaglinide addition to metformin monotherapy on glycemic control in patients with type 2 diabetes.
Authors: Moses R , Slobodniuk R , Boyages S , Colagiuri S , Kidson W , Carter J , Donnelly T , Moffitt P , Hopkins H
Published: March 2007

OBJECTIVE: To compare the effect of repaglinide in combination with metformin with monotherapy of each drug on glycemic control in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 83 patients with type 2 diabetes who had inadequate glycemic control (HbA1c > 7.1%) when receiving the antidiabetic agent metformin were enrolled in this multicenter, double-blind trial. Subjects were randomized to continue with their prestudy dose of metformin (n = 27), to continue with their prestudy dose of metformin with the addition of repaglinide (n = 27), or to receive repaglinide alone (n = 29). For patients receiving repaglinide, the optimal dose was determined during a 4- to 8-week titration and continued for a 3-month maintenance period. RESULTS: In subjects receiving combined therapy, HbA1c was reduced by 1.4 +/- 0.2%, from 8.3 to 6.9% (P = 0.0016) and fasting plasma glucose by 2.2 mmol/l (P = 0.0003). No significant changes were observed in subjects treated with either repaglinide or metformin monotherapy in HbA1c (0.4 and 0.3% decrease, respectively) or fasting plasma glucose (0.5 mmol/l increase and 0.3 mmol/l decrease respectively). Subjects receiving repaglinide either alone or in combination with metformin, had an increase in fasting levels of insulin between baseline and the end of the trial of 4.04 +/- 1.56 and 4.23 +/- 1.50 mU/l, respectively (P < 0.02). Gastrointestinal adverse events were common in the metformin group. An increase in body weight occurred in the repaglinide and combined therapy groups (2.4 +/- 0.5 and 3.0 +/- 0.5 kg, respectively; P < 0.05). CONCLUSIONS: Combined metformin and repaglinide therapy resulted in superior glycemic control compared with repaglinide or metformin monotherapy in patients with type 2 diabetes whose glycemia had not been well controlled on metformin alone. Repaglinide monotherapy was as effective as metformin monotherapy.
Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome.
Authors: Ehrmann D A , Barnes R B , Rosenfield R L , Cavaghan M K , Imperial J
Published: March 2007

OBJECTIVE: NIDDM occurs commonly among women with polycystic ovary syndrome (PCOS). The prevalence and natural history of its precursor, impaired glucose tolerance (IGT), is less well known. The objective of this study was to characterize the prevalence and incidence of glucose intolerance in a large cohort of women with well-characterized PCOS. RESEARCH DESIGN AND METHODS: A total of 122 women with clinical and hormonal evidence of PCOS were recruited from the Medicine, Endocrinology, Gynecology, and Pediatrics Clinics at the University of Chicago. All women had a standard oral glucose tolerance test (OGTT) with measurement of glucose and insulin levels. A subset of 25 women were subsequently restudied with the aim of characterizing the natural history of glucose tolerance in PCOS. RESULTS: Glucose tolerance was abnormal in 55 (45%) of the 122 women: 43 (35%) had IGT and 12 (10%) had NIDDM at the time of initial study. The women with NIDDM differed from those with normal glucose tolerance in that they had a 2.6-fold higher prevalence of first-degree relatives with NIDDM (83 vs. 31%, P < 0.01 by chi 2) and were significantly more obese (BMI 41.0 +/- 2.4 vs. 33.4 +/- 1.1 kg/m2, P < 0.01). For the entire cohort of 122 women, there was a significant correlation between fasting and 2-h glucose concentrations (r = 0.76, P < 0.0001); among the subset with IGT, the fasting glucose concentration was poorly predictive of the 2-h level (r = 0.25, NS). After a mean follow-up of 2.4 +/- 0.3 years (range 0.5-6.3), 25 women had a second OGTT. The glucose concentration at 2 h during the second glucose tolerance test was significantly higher than the 2-h concentration during the first study (161 +/- 9 vs. 139 +/- 6 mg/dl, P < 0.02). CONCLUSIONS: The prevalence of IGT and NIDDM in women with PCOS is substantially higher than expected when compared with age- and weight-matched populations of women without PCOS. The conversion from IGT to NIDDM is accelerated in PCOS. The fasting glucose concentration does not reliably predict the glucose concentration at 2 h after an oral glucose challenge, particularly among those with IGT, the subgroup at highest risk for subsequent development of NIDDM. We conclude that women with PCOS should periodically have an OGTT and must be closely monitored for deterioration in glucose tolerance.
Perinatal risk factors for childhood type 1 diabetes in Europe. The EURODIAB Substudy 2 Study Group.
Authors: Dahlquist G G , Patterson C , Soltesz G
Published: March 2007

OBJECTIVE: To explore whether perinatal factors are associated with the development of childhood type 1 diabetes. RESEARCH DESIGN AND METHODS: We studied hospital records from 892 cases of childhood type 1 diabetes compared with 2,291 population-based control subjects in seven study centers in Europe. RESULTS: In a pooled analysis incorporating stratification by center, we confirmed the previous findings that older maternal age, maternal preeclampsia, neonatal respiratory disease, and jaundice caused by blood group incompatibility are significant risk factors for type 1 diabetes, whereas being a firstborn child, having a low birth weight, or having a short birth length were protective. Cesarean section delivery and neonatal infectious diseases were not significantly associated with the risk of type 1 diabetes in this study. The strongest association was found for blood group incompatibility (AB0 and Rh factor) with an odds ratio (OR) of 2.96 (95% CI 1.88-4.65). AB0 incompatibility (OR = 3.92) was a more common and also a stronger risk factor than Rh incompatibility (OR = 1.62). The effect of AB0 blood group incompatibility was independent of treatment effects in logistical regression analysis. CONCLUSIONS: Different perinatal events are associated with an increased risk of type 1 diabetes. The effect of maternal-child blood group incompatibility is strong and indicates a true effect that must be further explored.
Immediate feedback of HbA1c levels improves glycemic control in type 1 and insulin-treated type 2 diabetic patients.
Authors: Cagliero E , Levina E V , Nathan D M
Published: March 2007

OBJECTIVE: Accurate and reliable HbA1c results can be obtained at the time of the office visit by using benchtop analyzers. We tested the hypothesis that immediately available HbA1c results could improve glycemic control by changing physician or patient behavior or both. RESEARCH DESIGN AND METHODS: A randomized controlled trial was conducted in 201 type 1 and insulin-treated type 2 diabetic patients attending an academic diabetes center. HbA1c levels, changes in insulin therapy, and use of health care resources were assessed during a 12-month follow-up period. RESULTS: HbA1c levels decreased significantly at 6 and 12 months in the immediate assay group (-0.57 +/- 1.44 and -0.40 +/- 1.65%, respectively; P < 0.01) but did not change in the control group (-0.11 +/- 0.79 and -0.19 +/- 1.16%, respectively; NS). The changes were similar for both type 1 and type 2 diabetic patients. There were no differences in the rates of hypoglycemic events or use of health care resources. CONCLUSIONS: In the setting of a controlled randomized trial, the immediate feedback of HbA1c results at the time of patient encounters resulted in a significant improvement of glycemic control at 6-month follow-up and persisted for the 12-month study. The introduction of this assay was positively received by both patients and physicians.
Effect of physician specialty on outcomes in diabetic ketoacidosis.
Authors: Levetan C S , Passaro M D , Jablonski K A , Ratner R E
Published: March 2007

OBJECTIVE: More than 100,000 people are hospitalized annually in the U.S. with diabetic ketoacidosis (DKA). Outcome differences have not been examined for these patients based on whether their primary care provider is a generalist or a diabetes specialist. The objective of this study was to investigate hospital charges and hospital length of stay (LOS) for patients with DKA according to the specialty of their primary care provider. RESEARCH DESIGN AND METHODS: We investigated all patients with a primary diagnosis of DKA during a 3.5-year period (n = 260) in a large urban teaching hospital. Hospital charges and LOS were studied regarding the specialty of the primary care provider. Demographic factors, severity of illness, laboratory data, and readmission rates were compared. RESULTS: Patients cared for by generalists and endocrinologists had a similar case mix and severity of DKA. The age-adjusted mean LOS for patients of generalists was 4.9 days (95% CI 4.5-5.4), and the mean LOS for patients of endocrinologists was 3.3 days (2.6-4.2) (P < 0.0043). Mean hospital charges differed (P < 0.0001) with an age- and sex-adjusted mean for patients of endocrinologists of $5,463 ($4,179-7,141) and a mean for patients of generalists of $10,109 ($9,151-11,166). The additional charges incurred by generalists were due in part to patients undergoing more procedures. No differences in diabetes-related complications occurred during admission, but the endocrinologist-treated group had a lower readmission rate for DKA during the study period than the generalist-treated group (2 vs. 6%, respectively) (P = 0.03). CONCLUSIONS: Endocrinologists provide more cost-effective care than generalists do when serving as primary care providers for patients hospitalized with DKA.
Optimized autoantibody-based risk assessment in family members. Implications for future intervention trials.
Authors: Bingley P J , Williams A J , Gale E A
Published: March 2007

OBJECTIVE: To determine the best autoantibody-based testing strategy for recruiting relatives for future intervention trials and to establish the role of islet cell antibodies (ICAs) within this strategy. RESEARCH DESIGN AND METHODS: ICAs, insulin autoantibodies (IAAs), GAD antibodies, and IA-2 antibodies were determined in serum samples at study entry of 3,655 non-diabetic first-degree relatives of patients with type 1 diabetes who were followed for a median of 5.5 years. The cumulative risk of diabetes associated with single and combined antibody marker levels of > or = 97.5th percentile in schoolchildren was calculated by using life-table analysis. RESULTS: Of the 26 relatives who developed insulin-requiring diabetes during follow-up, 16 were aged < 20 years and 7 were aged 20-39 years at study entry. Of the 23 cases aged < 40 years, 83% had IA-2 and/or GAD antibodies, and 87% had IAA and/or GAD antibodies > or = 97.5th percentile compared with 61% who had ICAs of > or = 5 Juvenile Diabetes Foundation units (JDF U). A two-step strategy with parallel testing for IA-2/GAD antibodies followed by IAA testing identified 50% of cases aged < 20 years and was associated with a 71% risk within 10 years. In subjects aged 20-39 years, this strategy conferred a 51% risk, whereas using ICAs as the second test gave 86% sensitivity and a 74% risk. Primary screening for IA-2 and/or GAD antibodies followed by testing for IAA and/or ICA antibodies achieved the highest sensitivity in both age-groups and conferred a 63% risk. In contrast, ICAs of > or = 20 JDF U (the inclusion criteria for the European Nicotinamide Diabetes Intervention Trial) gave 48% sensitivity and 35% risk. CONCLUSIONS: ICA testing can be replaced as a primary screening measure by IA-2/GAD or IAA/GAD antibody testing. The sensitivity of ICAs (used alone or in combination with IAAs) gives them a useful role in second-line testing. Combination testing could reduce the size of screening populations needed for recruitment in future intervention trials by approximately 50% compared with testing based on ICAs alone.
Glycemic control in diabetic American Indians. Longitudinal data from the Strong Heart Study.
Authors: Hu D , Henderson J A , Welty T K , Lee E T , Jablonski K A , Magee M F , Robbins D C , Howard B V
Published: March 2007

OBJECTIVE: To describe glycemic control and identify correlates of elevated HbA1c levels in diabetic American Indians participating in the Strong Heart Study, which is a longitudinal study of cardiovascular disease in American Indians in Arizona, Oklahoma, South Dakota, and North Dakota. RESEARCH DESIGN AND METHODS: This analysis is based on data from the baseline (1989-1992) and first follow-up (1994-1995) examinations of the Strong Heart Study. The 1,581 diabetic participants included in this analysis were aged 45-74 years at baseline, were diagnosed with diabetes before and at baseline, and had their HbA1c levels measured at follow-up. HbA1c was used as the index of glycemic control. Characteristics that may affect glycemic control were evaluated for cross-sectional and longitudinal relationships by analysis of covariance and multiple regression. RESULTS: There was no significant difference between median HbA1c at baseline (8.4%) and at follow-up (8.5%). Sex, age (inversely), and insulin and oral hypoglycemic agent therapy were significantly related to HbA1c levels in both the cross-sectional and longitudinal analyses. Current smoking, prior use of alcohol, and duration of diabetes were significant only for the cross-sectional data. Baseline HbA1c significantly and positively predicted HbA1c levels at follow-up. Comparison of HbA1c by therapy type shows that insulin therapy produced a significant decrease in HbA1c between the baseline and follow-up examinations. CONCLUSIONS: Glycemic control was poor among diabetic American Indians participating in the Strong Heart Study. Women, patients taking insulin or oral hypoglycemic agents, and younger individuals had the worst control of all the participants. Baseline HbA1c, and weight loss predicted worsening of control, whereas insulin therapy predicted improvement in control. Additional therapies and/or approaches are needed to improve glycemic control in this population.
Infant feeding, early weight gain, and risk of type 1 diabetes. Childhood Diabetes in Finland (DiMe) Study Group.
Authors: Hyppönen E , Kenward M G , Virtanen S M , Piitulainen A , Virta-Autio P , Tuomilehto J , Knip M , Akerblom H K
Published: March 2007

OBJECTIVE: To evaluate whether the increased risk of type 1 diabetes conferred by an early introduction of cow's milk supplements can be mediated by accelerated growth in formula-fed infants. RESEARCH DESIGN AND METHODS: All children < or = 14 years of age who were diagnosed with type 1 diabetes from September 1986 to April 1989 were invited to participate in the study. Birth date- and sex-matched control children were randomly selected from the Finnish Population Registry. At least three weight measurements from the first year of life were obtained for 435 full-term diabetic subjects and 386 control subjects from well-baby clinics and school health care units. RESULTS: Increase in body weight was greater in the diabetic girls than in the control girls, and the difference increased from 111 g (95% CI 0-218, P = 0.04) at 1 month of age to 286 g (95% CI 123-450, P = 0.0006) at 7 months. For boys, the difference in weight between the diabetic subjects and the control subjects remained stable during infancy (difference 95 g, 95% CI-2-205, P = 0.09). Increased weight was associated on average with a 1.5-fold risk of type 1 diabetes. Early introduction of formula feeding (< 3 vs. > or = 3 months) was also associated with an increased risk of type 1 diabetes after adjustment for the individual weight gain curve (adjusted odds ratio 1.53, 95% CI 1.1-2.2). No evidence for interaction was observed. CONCLUSIONS: These observations indicate that an early exposure to cow's milk formula-feeding and rapid growth in infancy are independent risk factors of childhood type 1 diabetes.
Relationship of endothelial function to birth weight in humans.
Authors: McAllister A S , Atkinson A B , Johnston G D , McCance D R
Published: March 2007

OBJECTIVE: Low birth weight has been associated with hyperlipidemia, hypertension, diabetes, and coronary heart disease in adult life, but the precise mechanism is debated. The endothelium is thought to play a pivotal role in each of the above conditions with abnormalities being detectable before the development of overt disease. To investigate the possibility that endothelium has a role in mediating the excessive risk of adult vascular disease associated with low birth weight, endothelial function was assessed in young healthy adults who were either of low or normal birth weight at term. RESEARCH DESIGN AND METHODS: Twelve low birth weight (2.2 +/- 0.05 kg, mean +/- SEM) subjects (six men/six women; age 28 +/- 0.2 years) and twelve age- and sex-matched normal birth weight (3.3 +/- 0.07 kg) control subjects were studied. The L-arginine-nitric oxide pathway was assessed in the forearm vascular bed by using venous occlusion plethysmography during intra-arterial brachial infusion of acetylcholine, sodium nitroprusside, norepinephrine, and NG-monomethyl-L-arginine (L-NMMA). Von Willebrand factor, a noninvasive marker of endothelial dysfunction, was also measured. Comparisons were made using Student's t test. RESULTS: Von Willebrand factor was significantly elevated in low birth weight compared with normal birth weight subjects (136.9 +/- 12.7 vs. 95.6 +/- 9.5%; P = 0.016). The groups did not differ in the responses to acetylcholine (P = 0.76), sodium nitroprusside (P = 0.84), norepinephrine (P = 0.21), or L-NMMA (P = 0.35). CONCLUSIONS: The finding of elevated von Willebrand factor in low birth weight subjects is suggestive of endothelial cell injury but does not appear to be associated with dysfunction of the L-arginine-nitric oxide pathway.
Impaired fasting glucose and the risk of hypertension in Japanese men between the 1980s and the 1990s. The Osaka Health Survey.
Authors: Suematsu C , Hayashi T , Fujii S , Endo G , Tsumura K , Okada K , Morii H
Published: March 2007

OBJECTIVE: To determine whether impaired fasting glucose (IFG) increased the risk for hypertension in two large Japanese cohorts during the different time periods. RESEARCH DESIGN AND METHODS: We prospectively investigated two Japanese cohorts: a 1980s population, comprising 4,130 normotensive and nondiabetic men aged 35-60 years entered between 1981 and 1983, and a 1990s population, comprising 4,319 normotensive and nondiabetic men aged 35-60 years entered between 1991 and 1992. Data on lifestyle factors were obtained from questionnaires. IFG was defined as a fasting plasma glucose level > or = 110 and < 126 mg/dl. RESULTS: During the 4-year observation period, 708 cases of hypertension were confirmed in the 1980s and 848 cases were confirmed in the 1990s. In both the 1980s and 1990s populations, IFG was associated with the risk of hypertension. The frequency of IFG in men in the 1990s group was twice as high as that in the 1980s group. The multivariate-adjusted odds ratio (OR) of hypertension was 1.54 (95% CI, 1.01-2.34) for men with IFG in the 1980s population and 1.73 (1.31-2.29) in the 1990s population, compared with those without IFG in the two populations. In the 1990s population, among lean men with a BMI < or = 23 kg/m2, men with IFG had a multivariate-adjusted OR of hypertension of 2.31 (1.46-3.65) compared with those without IFG. CONCLUSIONS: This study demonstrated direct correlation between IFG and hypertension and greater incidence of this hypertension in the 1990s group than in the 1980s group.
HDL cholesterol subfractions and risk of developing type 2 diabetes among Pima Indians.
Authors: Fagot-Campagna A , Knowler W C , Narayan K M , Hanson R L , Saaddine J , Howard B V
Published: March 2007

OBJECTIVE: To examine the relationships between HDL cholesterol subfractions and the incidence of type 2 diabetes and to evaluate potential sex differences in these relationships. RESEARCH DESIGN AND METHODS: Proportional hazards analyses were performed to examine the relationships between HDL subfractions and the development of type 2 diabetes in Pima Indian women and men. Results were controlled for age, BMI, systolic blood pressure, and 2-h glucose. RESULTS: Some 54 of 123 women and 25 of 50 men developed type 2 diabetes during a mean follow-up of 10 (2-19) years. For women, in separate models, high levels of total HDL, HDL2a, and HDL3 were negatively associated with incidence of type 2 diabetes; results were unchanged in models further controlled for fasting insulin level or alcohol consumption. For men, the results were inconsistent and associated with wide confidence intervals; high total HDL and HDL3 were positively associated with incidence of type 2 diabetes in models further controlled for fasting insulin level, but the risk estimates were attenuated in models further controlled for alcohol consumption. CONCLUSIONS: High levels of total HDL, HDL2a, and HDL3 were potential protective factors against type 2 diabetes in women after accounting for alcohol consumption and insulin resistance. High levels of total HDL and HDL3 were predictive of type 2 diabetes in men; the relationship in men appeared to be due to an association with alcohol consumption. The sex differences in the effects of HDL cholesterol may be related to the effects of sex hormones or lipoproteins.
Correlation of imaging techniques to histopathology in patients with diabetic foot syndrome and clinical suspicion of chronic osteomyelitis. The role of high-resolution ultrasound.
Authors: Enderle M D , Coerper S , Schweizer H P , Kopp A E , Thelen M H , Meisner C , Pressler H , Becker H D , Claussen C , Häring H U , Luft D
Published: March 2007

OBJECTIVE: To investigate the role of ultrasound in the diagnosis of osteomyelitis in the diabetic foot compared with magnetic resonance imaging (MRI), bone scintigraphy (BS), and plain film radiography (PFR). RESEARCH DESIGN AND METHODS: We investigated 19 consecutive diabetic patients (2 women, 17 men, age 60.7 +/- 9.8 years, BMI 27.0 +/- 3.8 kg/m2) with clinical suspicion of bone infection of the foot. A high-resolution ultrasound system (Esaote/Biosound, Munich) with a linear array transducer up to 13.0 MHz was used. The prospective and blinded results of each method were compared with histopathology as the reference method after metatarsal resection. RESULTS: In 14 of 19 patients, histopathology confirmed osteomyelitis. Ultrasound showed a sensitivity of 79% (PFR, 69%; BS, 83%; MRI, 100%), a specificity of 80% (PFR, 80%; BS, 75%; MRI, 75%), a positive predictive value of 92% (PFR, 90%; BS, 91%; MRI, 93%), and a negative predictive value of 57% (PFR, 50%; BS, 60%; MRI, 100%). CONCLUSIONS: Our data indicate that ultrasound might have a better diagnostic power for detecting chronic osteomyelitis in the diabetic foot than PFR and has similar sensitivity and specificity as BS. MRI is superior to the other three methods. We conclude that the use of ultrasound in the management of the diabetic foot is worthy of further investigation.
Postural characteristics of diabetic neuropathy.
Authors: Oppenheim U , Kohen-Raz R , Alex D , Kohen-Raz A , Azarya M
Published: March 2007

OBJECTIVE: To explore the posturographic correlates of diabetic neuropathy by comparing the performances of three groups of diabetic patients (severe, moderate, and absent neuropathy) with those of normal subjects and four clinical control groups. RESEARCH DESIGN AND METHODS: Using the Interactive Balance System (Tetrax, Ramat Gan, Israel), based on the assessment of the interaction of vertical pressure fluctuations on four independent platforms, one for each heel and toe part, respectively, posturographic examinations were given to 28 diabetic patients (8 with severe, 12 with moderate, and 8 with no peripheral neuropathy), 30 normal control subjects, and a clinical control group of 52 patients (14 with stage II Parkinson's disease, 13 with brain damage, 7 with whiplash, and 19 with peripheral vestibular pathology). The following posturographic parameters were evaluated; 1) general stability; 2) Fourier analysis showing patterns of sway intensity within eight frequency bands between 0.1 and 3 Hz; 3) weight distribution; 4) synchronization of sway; and 5) performance patterns for eight positions, requiring closure of eyes and standing on an elastic surface, as well as left, right, back, and downward head turns. RESULTS: For positions with closed eyes, diabetic patients with severe and moderate neuropathy were significantly less stable than normal subjects and diabetic patients without neuropathy, but diabetic patients with severe and moderate neuropathy turned out to be as equally unstable as clinical control subjects. However, for sway intensity within the band of 0.5 to 1.00 Hz on positions with lateral head turn with occluded vision, neuropathic diabetic patients performed significantly worse than did both normal and clinical control subjects. The same posturographic parameter also differed significantly between normal subjects and diabetic patients without neuropathy. CONCLUSIONS: As reported in previous studies, general instability in diabetic neuropathy is not a sufficiently characteristic correlate of the syndrome. On the other hand, spectral analysis of sway on stressful positions involving head turning appears to differentiate diabetic neuropathy from other disorders involving postural disturbances.
Increased intimal-medial thickness in newly detected type 2 diabetes: risk factors.
Authors: Temelkova-Kurktschiev T S , Koehler C , Leonhardt W , Schaper F , Henkel E , Siegert G , Hanefeld M
Published: March 2007

OBJECTIVE: To examine carotid intimal-medial thickness (IMT) and its determinants in newly detected type 2 diabetic subjects, classified according to the new criteria of the American Diabetes Association, in comparison with age- and sex-matched control subjects with normal glucose tolerance. RESEARCH DESIGN AND METHODS: This study was case-controlled, with matched pairs for 71 newly diagnosed type 2 diabetic individuals. Subjects aged 40-70 years were recruited from a risk population for diabetes seen in the Risk Factors in IGT for Atherosclerosis and Diabetes (RIAD) Study. Standard risk factors, 75-g oral glucose tolerance test with real insulin, proinsulin, and C-peptide, and ultrasound measurement of the IMT of the common carotid artery were performed. RESULTS: The diabetic subjects, both men and women, displayed carotid intimal-medial thickening, even in the subgroup with fasting plasma glucose between 7.0 and 7.8 mmol/l. HbA1c was significantly increased in the diabetic patients (6.33 vs. 5.48%). Insulin, proinsulin, and C-peptide were also significantly higher. Among the coronary risk factors, triglycerides and plasminogen activator inhibitor were significantly increased. After age and sex adjustment. IMT in the diabetic group was correlated to triglycerides and the total-to-HDL cholesterol ratio. In the total group, IMT was significantly correlated to blood pressure, 2-h glucose in oral glucose tolerance testing, triglycerides, albuminuria, and the total-to-HDL cholesterol ratio, and inversely correlated to HDL cholesterol. No independent determinant of IMT was found in the diabetic group by multivariate analysis. CONCLUSIONS: Newly detected type 2 diabetic patients exhibit a higher degree of early atherosclerosis than normal glucose-tolerant subjects matched for age and sex. Our data suggest that hyperglycemia, together with a clustering of risk factors, and in particular dyslipidemia, may cause intimal-medial thickening in the early phases of diabetes.
Plasma leptin concentrations in Pima Indians living in drastically different environments.
Authors: Fox C , Esparza J , Nicolson M , Bennett P H , Schulz L O , Valencia M E , Ravussin E
Published: March 2007

OBJECTIVE: Plasma leptin, an important signal for the regulation of energy stores, is known to be influenced by many hormonal factors, but may also be affected by behavioral and environmental factors. The purpose of this study was to investigate the impact of lifestyle (diet composition, level of physical activity) on plasma leptin concentrations among Pima Indians living in drastically different environments. RESEARCH DESIGN AND METHODS: We studied 224 Mexican Pima Indians (115 women, 109 men) living a traditional lifestyle in a remote, mountainous area of northwest Mexico and 418 U.S. Pima Indians (281 women, 137 men) living a North American lifestyle on the Gila River Indian Reservation in Arizona. We hypothesized that the absolute value of leptin would be lower in Mexican Pima Indians because of their lower percent body fat, but could be further influenced by their lifestyle, independent of body composition. RESULTS: Leptin concentration (enzyme-linked immunosorbent assay [ELISA]) was strongly correlated with percent fat (bioimpedance) in Mexican Pima Indians (r = 0.83, P < 0.0001) and U.S. Pima Indians (r = 0.86, P < 0.0001). Among U.S. Pima Indians, independent of percent fat, subjects with type 2 diabetes had lower leptin than nondiabetic subjects (difference = 6.9 +/- 1.0 ng/ml, P < 0.002). Among nondiabetic subjects, Mexican Pima Indians had lower absolute leptin concentrations than U.S. Pima Indians, but higher after adjustment for percent body fat, waist circumference, age, and sex. In a subset of 70 pairs of subjects matched for sex and percent body fat, leptin concentration was 4.4 +/- 1.0 ng/ml (P < 0.0001) higher in Mexican Pima Indians versus U.S. Pima Indians. CONCLUSIONS: These results suggest that independent of body composition, leptin concentration may be increased by environmental factors, such as a high-carbohydrate diet and a high level of physical activity.
Effect of selective screening for gestational diabetes.
Authors: Williams C B , Iqbal S , Zawacki C M , Yu D , Brown M B , Herman W H
Published: March 2007

OBJECTIVE: To estimate the percentage of pregnant women who would not be screened and the percentage of women with gestational diabetes mellitus (GDM) who would possibly remain undiagnosed if the American Diabetes Association's (ADA's) new selective screening recommendations are used rather than universal screening for GDM. RESEARCH DESIGN AND METHODS: Since 1987, the University of Michigan Health System has performed universal screening for GDM. In 1997, the ADA recommended that women having all four of the following characteristics need not be screened: age < 25 years, not members of an ethnic/racial group with a high prevalence of diabetes, normal body weight, and no family history of diabetes. We studied a random sample of the 25,118 deliveries at the University of Michigan between 1987 and 1997 to determine the prevalence of these four characteristics in our obstetric population. We also studied the prevalence of these four characteristics in 200 women who were diagnosed with GDM in the Endocrine Testing Unit and delivered at the University of Michigan between 1987 and 1997. RESULTS: Approximately 10-11% of women who delivered possessed all four low-risk characteristics and would not have been screened for GDM according to the new ADA recommendations. Only 4% of women (5 of 141) with GDM who delivered and for whom data on all four characteristics were reported possessed all four low-risk characteristics and would not have been screened. CONCLUSIONS: If the new ADA selective screening recommendations are used, few women with GDM will be missed (4%) but approximately 90% of pregnant women will still need to be screened for GDM.
Lispro Mix25 insulin as premeal therapy in type 2 diabetic patients.
Authors: Koivisto V A , Tuominen J A , Ebeling P
Published: March 2007

OBJECTIVE: Insulin Mix25 is a new premixed insulin analog containing 25% insulin lispro and 75% neutral protamine lispro (NPL) suspension (NPL insulin). The aim of the study was to compare serum glucose and insulin responses after breakfast in type 2 diabetic patients who received Mix25, premixed regular/NPH (30%/70%), or NPH insulin before the meal. RESEARCH DESIGN AND METHODS: We studied 22 type 2 diabetic patients of age 62 +/- 1 years, BMI 30 +/- 1 kg/m2, duration of diabetes 15 +/- 2 years, duration of insulin therapy 6 +/- 1 years, insulin dose 65 +/- 6 U/day, and HbA1c 7.9 +/- 0.2%. Ten healthy individuals (age 56 +/- 1 years, BMI 28 +/- 1 kg/m2) served as control subjects. Each patient (except healthy subjects, who were studied once each) was studied three times in a double-blind, randomized fashion. After an overnight fast, the patients received 36 +/- 4 U of test insulin. Ten minutes after insulin injection, the patients ingested a breakfast meal (512 kcal, 60% carbohydrate, 20% fat, and 20% protein), identical in all studies. Blood samples were taken before and at 10- to 30-min intervals for 240 min after the breakfast meal. RESULTS: The peak rise in serum glucose was lower after Mix25 (76 +/- 7 mg/dl) than after 30/70 (94 +/- 5 mg/dl, P < 0.05) or NPH (113 +/- 4 mg/dl, P < 0.005) insulin. The incremental area under the serum glucose curve was 36% smaller after Mix25 than after 30/70 (P < 0.01) and 56% smaller than after NPH (P < 0.005) insulin. The peak rise in serum insulin concentration was higher after Mix25 (103 +/- 18 mU/l) than after 30/70 (87 +/- 13 mU/l, P < 0.05) or NPH (62 +/- 12 mU/l, P < 0.01) insulin. The incremental area under the serum insulin curve was higher after Mix25 than after 30/70 during the first 2-3 h (P < 0.02), but the difference disappeared by the end of the 4-h follow-up period. After Mix25 injection, there was an inverse correlation between the glucose response to a meal and insulin dose (r = -0.56, P < 0.01) or the incremental area under the serum insulin curve (r = -0.39, P < 0.05). No such correlations were observed with the other insulins. CONCLUSIONS: Because of its faster initial absorption rate, the new premixed insulin analog Mix25 reduces blood glucose response to a breakfast meal in type 2 diabetic patients compared with premixed 30/70 (regular/NPH) or NPH insulin.
Use of insulin lispro in continuous subcutaneous insulin infusion treatment. Results of a multicenter trial. German Humalog-CSII Study Group.
Authors: Renner R , Pfützner A , Trautmann M , Harzer O , Sauter K , Landgraf R
Published: March 2007

OBJECTIVE: Insulin lispro is an analog of human insulin with a faster onset and a shorter duration of action than regular human insulin. Efficacy and tolerability of insulin lispro in continuous subcutaneous insulin infusion (CSII) treatment were assessed in an open randomized crossover trial comparing insulin lispro and regular human insulin, both applied with insulin pumps. RESEARCH DESIGN AND METHODS: A total of 113 type 1 patients (60 male, 53 female, age [mean +/- SD] 37 +/- 12 years, duration of diabetes 19 +/- 9 years) participated in this open, randomized crossover study. Both insulins were applied for 4 months each with the appropriate intervals between the prandial insulin bolus and the meal (human insulin: 30 min; lispro: 0 min). Observation parameters were HbA1c, daily and postprandial blood glucose profiles, adverse events, rate of hypoglycemic and hyperglycemic events, number of catheter obstructions, and treatment satisfaction as assessed with an international validated questionnaire. RESULTS: The patients were well controlled with a mean HBA1c of 7.24 +/- 1.0% at baseline. HbA1c decreased in both treatment periods, but it was better during insulin lispro treatment (insulin lispro: 6.8 +/- 0.9%, regular human insulin: 6.9 +/- 1.0%, Friedman's rank-sum test: P < 0.02). In addition, the 1-h and 2-h postprandial rises in blood glucose were significantly lower (P < 0.001 for each meal) with insulin lispro, resulting in smoother daily glucose profiles as compared with regular human insulin. No significant differences were reported for the rate of hypoglycemia (mean +/- SD [median]: insulin lispro 12.4 +/- 13.9 [8], regular human insulin 11.0 +/- 11.2 [8]), for the rate of catheter obstructions (42 events in each treatment arm), and for the number and type of adverse events. No severe case of ketoacidosis was seen during insulin lispro treatment, whereas one case was reported during therapy with regular human insulin. Treatment satisfaction was better when patients were treated with insulin lispro. CONCLUSIONS: Insulin lispro is a suitable and very convenient pump insulin that may result in an improvement of long-term glucose control during CSII treatment. Its safety profile does not differ from that of regular human insulin.
Apolipoprotein(B) identifies dyslipidemic phenotypes associated with cardiovascular risk in normocholesterolemic type 2 diabetic patients.
Authors: Wägner A M , Pérez A , Calvo F , Bonet R , Castellví A , Ordóñez J
Published: March 2007

OBJECTIVE: Apolipoprotein(B) [apo(B)] reflects the total mass of atherogenic particles (VLDL, IDL, and LDL), and its increase is associated with cardiovascular disease independently of LDL cholesterol (LDLc) levels. Apo(B) determination has been recently standardized, but attention to regional reference limits is advisable. Our aim was to analyze the frequency of dyslipidemic phenotypes, including those dependent on increased apo(B) in normocholesterolemic type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A total of 100 consecutively seen type 2 diabetic patients (63 men, 37 women; aged 59 +/- 11 years) were included, after excluding those on lipid-lowering therapy. Apo(B) cutoff (1.1 g/l) was obtained from a group of normolipidemic (47 men, 21 women) control subjects, and LDLc, triglycerides, and HDL cholesterol (HDLc) cutoff points were those from the National Cholesterol Education Program guidelines. LDLc levels were obtained by ultracentrifugation if triglyceride levels were > 3.45 mmol/l; otherwise, they were calculated (Friedwald). Apo(B) levels were measured by immunoturbidimetry. RESULTS: Normocholesterolemia (LDLc < 4.13 mmol/l) appeared in 75 of the 100 patients, of whom 55 were normo- and 20 hypertriglyceridemic. Hyperapolipoprotein(B) [hyperapo(B)] was the most frequent lipid disorder, present in 34 (45%) of the normocholesterolemic patients (22 normo- and 12 hypertriglyceridemic). Low HDLc levels were more prevalent (53%) in patients with hyperapo(B) than in the rest (24%). CONCLUSIONS: Hyperapo(B) was found in almost half of the normocholesterolemic type 2 diabetic patients and was frequently associated with low HDLc levels and hypertriglyceridemia. Thus, given its independent association with cardiovascular disease and that it identifies high-risk phenotypes in normocholesterolemic diabetic patients apo(B) should be used to evaluate the lipidic pattern of these patients.
Pharmacologic induction of weight loss to treat type 2 diabetes.
Authors: Redmon J B , Raatz S K , Kwong C A , Swanson J E , Thomas W , Bantle J P
Published: March 2007

OBJECTIVE: Most individuals with type 2 diabetes are overweight, and weight loss for them is an important therapeutic objective. However, usual weight-loss strategies have generally not produced sustained weight loss. Pharmacologic agents to assist weight loss might be useful, but no long-term data on their effectiveness and safety in patients with type 2 diabetes are available. We therefore initiated a 2-year placebo-controlled trial of the weight-loss medications fenfluramine and phentermine in type 2 diabetic subjects. RESEARCH DESIGN AND METHODS: A total of 44 overweight (> 120% ideal body weight) subjects with type 2 diabetes were enrolled in a randomized, placebo-controlled, double-blind trial of fenfluramine and phentermine. All subjects received intensive nutrition counseling, an exercise prescription, and instruction in behavior modification. Subjects were randomly assigned to 20 mg fenfluramine three times a day and 37.5 mg phentermine daily (n = 23) or dual placebos (n = 21). Diabetes medications were adjusted as necessary to achieve glycemic goals. Changes in weight, glycemia, lipemia, and blood pressure were assessed every 2 months, as were adverse events. In September 1997, when fenfluramine was withdrawn from the U.S. market, fenfluramine was stopped in all subjects. Thus the length of drug treatment varied, but 16 subjects (8 in each group) reached 12 months of treatment. Only data obtained before the withdrawal of fenfluramine are included in this report. RESULTS: A study termination, diabetes medications had been reduced in 1 subject in the placebo group (5%) and 11 subjects in the drug treatment group (52%) (P = 0.005). Drug treatment resulted in significant reductions in body weight, BMI, and HbA1c at all time points through 6 months. Changes in weight at 6 months were -2.7 +/- 1.4 kg (mean +/- SEM) with placebo treatment and -9.6 +/- 1.5 kg with drug treatment (P = 0.003). Even though more subjects in the drug treatment group required reductions in diabetes medications, at 6 months, changes in HbA1c were -0.3 +/- 0.2% with placebo treatment and -1.6 +/- 0.3% with drug treatment (P = 0.002). Fasting plasma glucose and triglycerides were significantly reduced at some time points with drug treatment. No serious adverse events attributable to study medications were observed. CONCLUSIONS: Premature study termination decreased the power of our study at later time points. However, our data suggest that weight loss medications are an effective treatment for type 2 diabetes during active weight loss. Whether the benefit persists after weight loss has stopped remains to be determined.
How valid is fasting plasma glucose as a parameter of glycemic control in non-insulin-using patients with type 2 diabetes?
Authors: Bouma M , Dekker J H , de Sonnaville J J , van der Does F E , de Vries H , Kriegsman D M , Kostense P J , Heine R J , van Eijk J T
Published: March 2007

OBJECTIVE: To assess the value of fasting blood glucose as a parameter for glycemic control in type 2 diabetic patients not using insulin. RESEARCH DESIGN AND METHODS: In 1,020 type 2 diabetic patients treated with diet or oral hypoglycemic agents (OHAs), measurements of fasting plasma glucose (FPG) and HbA1c were taken. In 617 patients, the measurement could be repeated after 3 months. Cross-sectional correlation coefficients were calculated for the association between HbA1c and FPG. Receiver-operating characteristic (ROC)-curve analyses were applied to examine the performance of FPG as a diagnostic test for HbA1c. Longitudinally, the change in FPG was compared with the change in HbA1c, with both correlation measures and ROC curve analyses. RESULTS: Correlation coefficients between HbA1c and FPG and between FPG change and HbA1c change were 0.77 and 0.65, respectively. ROC curve analysis showed that HbA1c is difficult to predict from FPG values: 66% of the patients with good HbA1c (< 7.0%) were identified as such by FPG values < 7.8 mmol/l. As a test for HbA1c change, FPG change performed moderately: the highest combined values of sensitivity and specificity (87.7 and 57%, respectively) were reached at a cutoff point of zero in the range of FPG change values. CONCLUSIONS: FPG and HbA1c values that do not correspond are not rare in type 2 diabetic patients on diet or OHA treatment. HbA1c is difficult to predict from FPG values, and even more difficult is the prediction of HbA1c changes from FPG changes.
Incidence of lactic acidosis in metformin users.
Authors: Stang M , Wysowski D K , Butler-Jones D
Published: March 2007

OBJECTIVE: The purpose of this study was to determine the incidence of lactic acidosis in a geographically defined population of metformin users. RESEARCH DESIGN AND METHODS: The study was based on a historical cohort from the Saskatchewan Health administrative databases. Individuals with a metformin prescription dispensed between 1980 and 1995 inclusive were eligible for the cohort. Person-years of exposure were calculated. Cases were defined by hospital discharge with a diagnosis of acidosis (International Classification of Diseases, Ninth Revision code: 276.2) and confirmation by chart review of a blood lactate level > or = 5 mmol/l. Death registrations of individuals dying within 120 days of a metformin prescription were also reviewed. RESULTS: During the study period, 11,797 residents received one or more metformin prescriptions, resulting in 22,296 person-years of exposure. There were 10 subjects who had hospital discharges with a diagnosis of acidosis. However, primary record review revealed only two cases with laboratory findings of elevated blood lactate levels, for an incidence rate of 9 cases per 100,000 person-years of metformin exposure. In both cases, other factors besides metformin could have contributed to the lactic acidosis. No additional cases were found on review of death registrations. CONCLUSIONS: From 1980 through 1995, the incidence rate of lactic acidosis was 9 per 100,000 person-years (95% CI 0-21) in patients dispensed metformin in Saskatchewan, Canada. This incidence rate was derived from a population with complete ascertainment of hospitalizations and deaths associated with lactic acidosis in metformin users. It is similar to previously published rates based on passive reporting of cases, and it is well below the lactic acidosis rate of 40-64 per 100,000 patient-years in patients prescribed phenformin.
Birth weight of women with gestational diabetes.
Authors: Moses R G , Moses J , Knights S
Published: March 2007

OBJECTIVE: Epidemiological observations have suggested a relationship between type 2 diabetes and a low birth weight. However, there are many confounding variables and problems with retrospective data collection. Women with gestational diabetes mellitus (GDM), who are likely to develop type 2 diabetes in the future, may help clarify these observations. RESEARCH DESIGN AND METHODS: Consecutive women with GDM (n = 138) were included in the study if they had a singleton pregnancy delivered between 37 and 41 weeks of gestation, if they had themselves been born in the local hospital, and if their own delivery data were available. With respect to their own births, a matched group was obtained by considering the next female delivery of the same gestational age. RESULTS: For women with GDM, the mean (+/- 1 SD) birth weight was 3,293 +/- 493 g and the ponderal index was 27.0 +/- 2.4. Their values were not significantly different from the matched group, which had a birth weight of 3,315 +/- 460 g and a ponderal index of 27.0 +/- 2.5. After adjusting for the gestational age of delivery, the birth weight of women with GDM did not show a U-shaped distribution. CONCLUSIONS: After adjustment for the gestational age of delivery, women with GDM do not themselves have either a lower or higher birth weight than a matched group. These data suggest that women with GDM are either not a good surrogate for investigating the relationship between birth weight and type 2 diabetes or that correction for the gestational age of delivery removes the most important confounding variable. It is also possible that modern dietary changes may have altered the relationship.