bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid and short-acting mealtime insulin secretion with nateglinide controls both prandial and mean glycemia.
Authors: Hanefeld M , Bouter K P , Dickinson S , Guitard C
Published: March 2007

OBJECTIVE: The objective of the study was to assess the efficacy and safety of four fixed doses of nateglinide compared with placebo in the treatment of patients with type 2 diabetes with focus on the prandial state. RESEARCH DESIGN AND METHODS: This randomized double-blind placebo-controlled multicenter study was conducted in 289 patients who received either nateglinide at doses of 30 mg (n = 51), 60 mg (n = 58), 120 mg (n = 63), or 180 mg (n = 57) or placebo (n = 60) before three main meals for 12 weeks. Levels of HbA1c, fasting plasma glucose (FPG), fructosamine, and plasma lipids were measured at predetermined intervals, and the effects of nateglinide on prandial glucose insulin, C-peptide, and triglyceride levels were measured after a liquid standard meal (Sustacal; Mead Johnson, Evansville, IN). Adverse events and hypoglycemic episodes were recorded. RESULTS: After a liquid meal challenge, nateglinide rapidly increased mealtime insulin levels within 30 min of drug intake and reduced mealtime glucose excursions without affecting triglyceride levels. At study end point, reduction of HbA1c levels was statistically significantly greater with nateglinide at doses of 60, 120, and 180 mg than placebo (-0.45, -0.62, and -0.64%, respectively; P<0.05). The mean level of FPG was significantly reduced versus placebo in the nateglinide 120-mg group only (-1.14 mmol/l P<0.01). Overall, nateglinide was well tolerated. CONCLUSIONS: This study demonstrated that nateglinide improves mealtime and mean glycemic control in a dose-dependent manner by restoring early insulin secretion phase. Nateglinide was well tolerated and is suitable for the treatment of patients with type 2 diabetes.
The influence of treatment modality and ethnicity on attitudes in type 2 diabetes.
Authors: Fitzgerald J T , Gruppen L D , Anderson R M , Funnell M M , Jacober S J , Grunberger G , Aman L C
Published: March 2007

OBJECTIVE: The study examines diabetes attitude differences by treatment modality (insulin vs. no insulin), race/ethnicity, and the interaction of these two variables for people with type 2 diabetes. RESEARCH DESIGN AND METHODS: Data were collected with the Diabetes Care Profile (DCP), an instrument that assesses psychosocial factors related to diabetes. Participants (n = 672) were recruited in the metropolitan Detroit, Michigan, area from 1993 to 1996. A total of 68% of these participants were African-Americans with type 2 diabetes, and 32% were Caucasians with type 2 diabetes. Analyses of covariance were performed to examine the effects of race/ethnicity, treatment, and their interaction for each DCP scale. RESULTS: The four patient categories (two ethnicities by two treatment modalities) differed by age, years with diabetes, education, and sex distribution. Treatment modality had a significant effect on 6 of the 16 DCP scales (Control, Social and Personal Factors, Positive Attitude, Negative Attitude, Self-Care Ability, and Exercise Barriers). Ethnicity was a significant effect for three scales (Control, Support, and Support Attitudes). The interaction of race/ethnicity and treatment modality was a significant effect for two related attitude scales (Positive Attitude and Negative Attitude). CONCLUSIONS: The results suggest that attitudes toward diabetes are similar for African-American and Caucasian patients with type 2 diabetes. The results also suggest that treatment modality has a greater effect on attitudes than either race/ethnicity or the interaction effect. However, Caucasian patients using insulin differed from the other patient groups by having the least positive and the most negative attitudes regarding diabetes.
Improved control of mealtime glucose excursions with coadministration of nateglinide and metformin.
Authors: Hirschberg Y , Karara A H , Pietri A O , McLeod J F
Published: March 2007

OBJECTIVE: Nateglinide, a new short-acting D-phenylalanine derivative for treating type 2 diabetes, reduces mealtime blood glucose excursions by physiologic regulation of insulin secretion. This study evaluated the pharmacokinetic and pharmacodynamic interactions of nateglinide and metformin in subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 12 type 2 diabetic subjects with the following baseline characteristics were enrolled: age, 56 +/- 13 years; BMI, 28.7 +/- 4.5 kg/m2; HbA1c, 8.4 +/- 1.3%; and fasting plasma glucose 13 +/- 2.8 mmol/l. All subjects had been previously treated with glyburide and were switched to metformin monotherapy for 3 weeks before study start. Subjects then randomly received, in combination with 500 mg metformin, either 120 mg nateglinide or placebo before meals for 1 day, followed by the alternate treatment 7 days later. After 1 week of washout from both drugs, subjects received 1 day of open-label nateglinide treatment. Plasma concentrations of glucose, insulin, nateglinide, and metformin were assessed frequently during inpatient periods. RESULTS: Postmeal plasma glucose levels were significantly lower in subjects treated with nateglinide plus metformin than in those treated with either drug alone (P < 0.001), especially after lunch and dinner. Coadministration of nateglinide and metformin did not affect the pharmacokinetics of either drug. All treatments were safe and well tolerated. CONCLUSIONS: Combination therapy with nateglinide and metformin was more effective than either treatment alone and did not result in any pharmacokinetic interactions. Coadministration of nateglinide and metformin appears to be an excellent option for treating patients with type 2 diabetes not controlled with monotherapy.
Meeting American Diabetes Association guidelines in endocrinologist practice.
Authors: Miller C D , Phillips L S , Tate M K , Porwoll J M , Rossman S D , Cronmiller N , Gebhart S S
Published: March 2007

OBJECTIVE: To determine whether American Diabetes Association (ADA) guidelines can be met in the context of routine endocrinology practice. RESEARCH DESIGN AND METHODS: Charts were reviewed for a group of patients who were examined in 1998, followed for > or = 1 year, and had two or more visits during that year. Process measures and metabolic outcomes were studied for patients with type 2 diabetes, and glycemic control was assessed for patients with type 1 diabetes. RESULTS: A total of 121 patients with type 2 diabetes had a mean age of 63 years, a mean BMI of 31 kg/m2, and a mean duration of diabetes of 12 years. Many had comorbidities or complications: 80% had hypertension, 64% had hyperlipidemia, 78% had neuropathy, 22% had retinopathy, and 21% had albuminuria. Management of type 2 diabetic patients was complex: 38% used oral hypoglycemic agents alone (54% of these were using two or more agents), 31% used oral hypoglycemic agents and insulin, and 26% used insulin alone; 42% of patients taking insulin therapy injected insulin three or more times per day. Within 12 months, 74% of patients had dilated eye examinations, 70% had lipid profiles, and 55% had urine albumin screening. Of the patients, 87% had a foot examination at their last visit. Blood pressure levels averaged 133/72 mmHg, cholesterol levels averaged 4.63 mmol/l, triglyceride levels averaged 1.99 mmol/l, HDL cholesterol levels averaged 1.24 mmol/l, and LDL cholesterol levels averaged 2.61 mmol/l. Random blood glucose levels averaged 8.0 mmol/l, and HbAlc levels averaged 6.9 +/- 0.1%. A total of 87% of patients had HbAlc levels < or = 8.0%. A total of 30 patients with type 1 diabetes had mean age of 44 years, a mean BMI of 26 kg/m2, and a mean duration of diabetes of 20 years. All type 1 diabetic patients used insulin and averaged 3.4 injections a day; their average HbAlc level was 7.1 +/- 0.2%, and 80% had HbAlc levels < or = 8.0%. CONCLUSIONS: Although endocrinologists must manage patients with multifaceted problems, complex treatment regimens yield glycemic control levels comparable with the Diabetes Control and Complications Trial and allow ADA guidelines to be met in a routine practice setting.
Self-monitoring of blood glucose: language and financial barriers in a managed care population with diabetes.
Authors: Karter A J , Ferrara A , Darbinian J A , Ackerson L M , Selby J V
Published: March 2007

OBJECTIVE: Self-monitoring of blood glucose (SMBG) is a cornerstone of diabetes care, but little is known about barriers to this self-care practice. RESEARCH DESIGN AND METHODS: This cross-sectional study examines SMBG practice patterns and barriers in 44,181 adults with pharmacologically treated diabetes from the Kaiser Permanente Northern California Region who responded to a health survey (83% response rate). The primary outcome is self-reported frequency of SMBG. RESULTS: Although most patients reported some level of SMBG monitoring, 60% of those with type 1 diabetes and 67% of those with type 2 diabetes reported practicing SMBG less frequently than recommended by the American Diabetes Association (three to four times daily for type 1 diabetes, and once daily for type 2 diabetes treated pharmacologically). Significant independent predictors of nonadherent practice of SMBG included longer time since diagnosis, less intensive therapy, male sex, age, belonging to an ethnic minority, having a lower education and neighborhood income, difficulty communicating in English, higher out-of-pocket costs for glucometer strips (especially for subjects with lower incomes), smoking, and excessive alcohol consumption. CONCLUSIONS: Considerable gaps persist between actual and recommended SMBG practices in this large managed care organization. A somewhat reduced SMBG frequency in subjects with linguistic barriers, some ethnic minorities, and subjects with lower education levels suggests the potential for targeted, culturally sensitive, multilingual health education. The somewhat lower frequency of SMBG among subjects paying higher out-of-pocket expenditures for strips suggests that removal of financial barriers by providing more comprehensive coverage for these costs may enhance adherence to recommendations for SMBG.
Use of insulin pump therapy at nighttime only for children 7-10 years of age with type 1 diabetes.
Authors: Kaufman F R , Halvorson M , Kim C , Pitukcheewanont P
Published: March 2007

OBJECTIVE: Because of age-related developmental and cognitive issues, children <10 years of age may not be able to wear an insulin pump safely when they are not under direct parental supervision. The purpose of this study was to determine if insulin pump therapy at nighttime only, when children are at home, could improve fasting and nighttime blood glucose levels without adverse effects. RESEARCH DESIGN AND METHODS: The study cohort consisted of 10 children aged 7-10 years. A randomized crossover design was used to compare nighttime-only pump usage from dinner and throughout the night, combined with a prebreakfast injection of intermediate-acting NPH and rapid-acting lispro insulin, with 3 insulin injections per day. Comparisons were made among mean blood glucose values and percentage of blood glucose levels within the target range (70-150 mg/dl) before meals, at bedtime, and at 3:00 A.M.; serum fructosamine levels; and scores on measures of adherence and fear of hypoglycemia. RESULTS: Compared with baseline levels, the use of the pump resulted in a significant decrease in the mean average (P < 0.001), breakfast (P < 0.0001), and 3:00 A.M. (P < 0.003) blood glucose levels. There was a decrease in the percentage of blood glucose values less than the target range (P < 0.01) and in fructosamine (P < 0.01) values and an increase in the percentage of blood glucose levels within the target range (P < 0.03). CONCLUSIONS: Nighttime-only insulin pump therapy may be a viable alternative that young children can use to improve glycemia when they are not capable of independently managing an insulin pump.
Fluoxetine for depression in diabetes: a randomized double-blind placebo-controlled trial.
Authors: Lustman P J , Freedland K E , Griffith L S , Clouse R E
Published: March 2007

OBJECTIVE: Depression is prevalent in patients with diabetes. It is associated with poor glycemic control and is linked to an increased risk for diabetic complications. In this study, we assessed the efficacy of fluoxetine for depression in patients with diabetes. RESEARCH DESIGN AND METHODS: Sixty patients with diabetes (type 1, n = 26; type 2, n = 34) and major depressive disorder entered an 8-week randomized placebo-controlled double-blind trial. Patients were given daily doses of fluoxetine (up to 40 mg/day). The Beck Depression Inventory (BDI) and Hamilton Rating Scale for Depression (HAMD) were used to measure the severity of depression and to determine the percentage of patients who achieved substantial improvement or complete remission. GHb levels were obtained to monitor glycemic control. RESULTS: Reduction in depression symptoms was significantly greater in patients treated with fluoxetine compared with those receiving placebo (BDI, -14.0 vs. -8.8, P = 0.03; HAMD, -10.7 vs. -5.2, P = 0.01). The percentage of patients achieving a significant improvement in depression per the BDI was also higher in the fluoxetine group (66.7 vs. 37.0%, P = 0.03). Additionally, trends toward a greater rate of depression remission (48.1 vs. 25.9%, P = 0.09 per the HAMD) and greater reduction in GHb (-0.40 vs. -0.07%, P = 0.13) were observed in the fluoxetine group. CONCLUSIONS: Fluoxetine effectively reduces the severity of depression in diabetic patients. Our study demonstrated that after only 8 weeks, this treatment also produced a trend toward better glycemic control.
Efficacy of injected liquid silicone in the diabetic foot to reduce risk factors for ulceration: a randomized double-blind placebo-controlled trial.
Authors: van Schie C H , Whalley A , Vileikyte L , Wignall T , Hollis S , Boulton A J
Published: March 2007

OBJECTIVE: To investigate the effectiveness of injecting liquid silicone in the diabetic foot to reduce risk factors for ulceration in a randomized double-blind placebo-controlled trial. RESEARCH DESIGN AND METHODS: A total of 28 diabetic neuropathic patients without peripheral vascular disease were randomized to active treatment with 6 injections of 0.2 ml liquid silicone in the plantar surface of the foot or to treatment with an equal volume of saline (placebo). No significant differences were evident regarding age or neuropathy status between the 2 groups. All injections were under the metatarsal heads at sites of calluses or high pressures. Barefoot plantar pressures (pedobarography) and plantar tissue thickness under the metatarsal heads (Planscan ultrasound device) were measured at baseline and at 3, 6, and 12 months after the first injection. Injection sites were photographed at all stages, and callus formation was scored as a change from baseline. Throughout the study, patients were treated by the same podiatrist for all podiatry treatment. RESULTS: Patients who received silicone treatment had significantly increased plantar tissue thickness at injection sites compared with the placebo group (1.8 vs. 0.1 mm) (P < 0.0001) and correspondingly significantly decreased plantar pressures (-232 vs. -25 kPa) (P < 0.05) at 3 months, with similar results at 6 and 12 months. A trend was noted toward a reduction of callus formation in the silicone-treated group compared with no change in the placebo group. CONCLUSIONS: The results confirm the efficacy of plantar silicone injections in reducing recognized risk factors associated with diabetic foot ulceration.
Hemodynamic effects of acute hyperglycemia in type 2 diabetic patients.
Authors: Marfella R , Nappo F , De Angelis L , Paolisso G , Tagliamonte M R , Giugliano D
Published: March 2007

OBJECTIVE: The aim of the present study was to evaluate the hemodynamic effects of acute hyperglycemia in type 2 diabetic patients and to see whether these effects are related to changes in nitric oxide (NO) availability. RESEARCH DESIGN AND METHODS: Twenty newly diagnosed complication-free diet-treated type 2 diabetic patients participated in the study. All patients underwent 3 hyperglycemic glucose clamps in random order: 1) the control study was performed with plasma glucose clamped at 18 mmol/l for 2 h; 2) the octreotide study with plasma insulin blocked at basal levels during the clamp; and 3) the L-arginine study with L-arginine (1 g/min) infused during the last 30 min of the clamp. A group of 8 patients also underwent a glutathione infusion (600 mg as an intravenous bolus followed by 5 mg/min infusion) during the clamp. RESULTS: During hyperglycemia, there were significant increments of systolic (sBP) (from 115.5 +/- 9.1 to 120.3 +/- 8.2 mmHg, P < 0.01) and diastolic (dBP) (from 70.3 +/- 7.8 to 79.7 +/- 5.3 mmHg, P < 0.01) blood pressure, as well as heart rate (from 75.2 +/- 7.8 to 80.8 +/- 5.4 beats/min, P < 0.01) and plasma catecholamines (P < 0.05). Squatting ratios, a measure of the baroreflex activity, significantly deteriorated after hyperglycemia (P < 0.01). The infusion of octreotide, used to avoid the possible confounding influence of insulin, did not change the hemodynamic effects of hyperglycemia. Glutathione, a free radical scavenger, completely prevented the vascular effects of hyperglycemia. L-Arginine produced a fall in sBP and dBP to baseline values and normalized squatting ratios. CONCLUSIONS: Acute hyperglycemia in newly diagnosed type 2 diabetic patients causes significant hemodynamic changes that are independent of endogenous insulin and are prevented by glutatione and reversed by L-arginine, suggesting an interference with endogenous NO availability. These observations could help explain the adverse cardiovascular effects of hyperglycemic spikes.
Asymptomatic bacteriuria may be considered a complication in women with diabetes. Diabetes Mellitus Women Asymptomatic Bacteriuria Utrecht Study Group.
Authors: Geerlings S E , Stolk R P , Camps M J , Netten P M , Hoekstra J B , Bouter K P , Bravenboer B , Collet J T , Jansz A R , Hoepelman A I
Published: March 2007

OBJECTIVE: To study the prevalence of and risk factors for asymptomatic bacteriuria (ASB) in women with and without diabetes. RESEARCH DESIGN AND METHODS: A total of 636 nonpregnant women with diabetes (type 1 and type 2) who were 18-75 years of age and had no abnormalities of the urinary tract, and 153 women without diabetes who were visiting the eye and trauma outpatient clinic (control subjects) were included. We defined ASB as the presence of at least 10(5) colony-forming units/ml of 1 or 2 bacterial species in a culture of clean-voided midstream urine from an individual without symptoms of a urinary tract infection (UTI). RESULTS: The prevalence of ASB was 26% in the diabetic women and 6% in the control subjects (P < 0.001). The prevalence of ASB in women with type 1 diabetes was 21%. Risk factors for ASB in type 1 diabetic women included a longer duration of diabetes, peripheral neuropathy, and macroalbuminuria. The prevalence of ASB was 29% in women with type 2 diabetes. Risk factors for ASB in type 2 diabetic women included age, macroalbuminuria, a lower BMI, and a UTI during the previous year. No association was evident between current HbA1c level and the presence of ASB. CONCLUSIONS: The prevalence of ASB is increased in women with diabetes and might be added to the list of diabetic complications in these women.
Effect of menopausal status on insulin-stimulated glucose disposal: comparison of middle-aged premenopausal and early postmenopausal women.
Authors: Toth M J , Sites C K , Eltabbakh G H , Poehlman E T
Published: March 2007

OBJECTIVE: Studies in animal models suggest that ovarian hormone deficiency is associated with the development of insulin resistance. In women, ovarian hormone levels are dramatically reduced after the menopause transition. However, the effect of the menopause transition on insulin sensitivity is unclear. Thus, we examined the effect of menopausal status on insulin sensitivity. RESEARCH DESIGN AND METHODS: Insulin-stimulated glucose disposal was measured in 43 middle-aged premenopausal women (47 +/- 3 years of age) during the luteal phase of the menstrual cycle and 40 early postmenopausal women (51 +/- 4 years; time since menopause, 21 +/- 13 months) using the hyperinsulinemic-euglycemic clamp technique. Body composition was measured by dual-energy X-ray absorptiometry and abdominal fat distribution by computed tomography RESULTS: No difference in fat-free mass (FFM) was found between groups. Total body (P < 0.01), subcutaneous abdominal (P < 0.05), and intra-abdominal (P < 0.01) adiposity were greater in postmenopausal women compared with premenopausal women. No differences in insulin-stimulated glucose disposal were found between premenopausal and postmenopausal women on an absolute basis (pre, 436 +/- 130 vs. post, 446 +/- 120 mg/min), when expressed relative to FFM (pre, 10.7 +/- 3.0 vs. post, 11.5 +/- 3.6 mg x kg(-1) FFM x min(-1)) or when statistically adjusted for FFM (pre, 436 +/- 125 vs. post, 445 +/- 126 mg/min). CONCLUSIONS: These results suggest that menopausal status does not affect insulin sensitivity, as measured by the hyperinsulinemic-euglycemic clamp technique.
Polymorphism of the tumor necrosis factor-alpha receptor 2 gene is associated with obesity, leptin levels, and insulin resistance in young subjects and diet-treated type 2 diabetic patients.
Authors: Fernández-Real J M , Vendrell J , Ricart W , Broch M , Gutiérrez C , Casamitjana R , Oriola J , Richart C
Published: March 2007

OBJECTIVE: Mice lacking the tumor necrosis factor-alpha receptor 2 (TNFR2) gene fed a high-fat diet gain less weight and display reduced leptin and insulin levels. In humans, plasma levels of the soluble fraction of TNFR2 (sTNFR2) circulate in proportion to the degree of insulin resistance. The purpose of this study was to evaluate a polymorphism in the 3' untranslated region of the TNFR2 gene on chromosome 1 in relation to BMI, leptin levels, and insulin resistance. RESEARCH DESIGN AND METHODS: Using single-strand conformation polymorphism, the polymorphism was analyzed in 107 nondiabetic subjects (60 women, 47 men) and in 110 consecutive patients with type 2 diabetes (79 women, 31 men). In a subset of 33 healthy subjects, insulin sensitivity (minimal model analysis) was also evaluated. RESULTS: Four alleles of the TNFR2 gene were identified (A1, A2, A3, and A4). BMI and serum leptin levels were significantly increased in young carriers of the A2 allele. Plasma sTNFR2 levels were similar among the different TNFR2 gene variants. However, in subjects who did not carry the A2 allele, in young subjects, and in women, plasma sTNFR2 levels were proportional to BMI and leptin levels. In the study sample, carriers of the A2 allele (n = 18) showed significantly increased BMI, fat mass, waist-to-hip ratio, serum total and VLDL triglyceride levels, and leptin levels and had a lower insulin sensitivity index than noncarriers of the A2 variant (n = 15). The frequency of the different alleles among diabetic subjects was similar to that in the control population. However, diet-treated diabetic subjects (n = 49) who were carriers of the A2 allele exhibited significantly higher BMI and leptin levels than diet-treated noncarriers of the A2 allele. CONCLUSIONS: The presence of the A2 allele in the TNFR2 gene may predispose subjects to obesity and higher leptin levels, which may in turn predispose them to insulin resistance or vice versa. The TNFR2 gene may be involved in weight-control mechanisms.
Delay in onset of awareness of acute hypoglycemia and of restoration of cognitive performance during recovery.
Authors: Evans M L , Pernet A , Lomas J , Jones J , Amiel S A
Published: March 2007

OBJECTIVE: To examine the time course for the onset of, and recovery from, acute hypoglycemia in healthy subjects. RESEARCH DESIGN AND METHODS: Eight healthy male volunteers were studied on 2 occasions in random order using a hyperinsulinemic (1.5 mU x kg(-1) x min(-1)) glucose clamp technique. During control studies, euglycemia (5.01 +/- 0.02 mmol/l) was maintained for 225 +/- 3 min. On the other occasion, after a euglycemic baseline period, arterialized plasma glucose was allowed to fall rapidly to 2.65 +/- 0.02 mmol/l, then maintained at this nadir for 90 min before euglycemia was rapidly restored. RESULTS: Cognitive function assessed by a battery of sensitive tests (4-choice reaction time, Stroop word, and color-word test) became impaired immediately at onset of hypoglycemia (P < 0.05 for all in the hypoglycemic study vs. those in the euglycemic study). Counterregulatory hormone responses (epinephrine, norepinephrine, glucagon, cortisol, and growth hormone) and symptomatic awareness of hypoglycemia (assessed by a questionnaire) were relatively delayed, being detected 20 min after the onset of hypoglycemia. There was no diminution (adaptation) of any responses, cognitive, humoral, or symptomatic, during sustained hypoglycemia. During recovery, the 4-choice reaction time continued to be abnormal even after resolution of symptomatic awareness (P = 0.025). CONCLUSIONS: During hypoglycemia, cognitive performance may become impaired before symptomatic awareness. During recovery from hypoglycemia, recovery of cognitive function lags behind the restoration of glucose levels and resolution of symptoms. Our findings have implications for the design of studies examining experimental hypoglycemia and need to be investigated in people with diabetes.
Sex differences in the association of endogenous sex hormone levels and glucose tolerance status in older men and women.
Authors: Goodman-Gruen D , Barrett-Connor E
Published: March 2007

OBJECTIVE: Some evidence suggests an inverse association between type 2 diabetes and androgens in men and a positive association between type 2 diabetes and androgens in women. The purpose of this community-based study was to evaluate sex differences in the association between endogenous total and bioavailable estrogen and testosterone levels and glucose tolerance status. RESEARCH DESIGN AND METHODS: We included in this study 775 men and 633 postmenopausal non-estrogen-using women, all > or =55 years of age (mean ages 72 and 75 years, respectively). A 75-g oral glucose tolerance test (OGTT) was administered to fasting subjects from 1984 to 1987, when sera were frozen for measurement of total and bioavailable hormone levels. Total testosterone and estradiol levels were measured by radioimmunoassay, and bioavailable hormone levels were determined using a modified ammonium-sulfate precipitation method. The association between steroid hormones and glucose tolerance status was tested. RESULTS: In sex-specific age- and BMI-adjusted analyses, men with impaired glucose tolerance (IGT) had significantly lower total testosterone levels. Women with IGT or type 2 diabetes had significantly higher bioavailable testosterone and total and bioavailable estradiol levels than those with normal glucose tolerance. Total testosterone and fasting plasma glucose were inversely associated in men (P = 0.0001), whereas bioavailable testosterone and estradiol were positively associated with fasting plasma glucose in women (P = 0.0001 and 0.001, respectively). CONCLUSIONS: Additional studies are needed to further develop the hormone-diabetes connection.
Impact of diabetes on coronary artery disease in women and men: a meta-analysis of prospective studies.
Authors: Lee W L , Cheung A M , Cape D , Zinman B
Published: March 2007

OBJECTIVE: Women are at a much lower risk of coronary disease mortality than men are. It is widely believed that diabetes "erases" this female advantage, increasing the risk of heart disease much more in women than in men. In reality, the extent of this increased risk is controversial, with studies showing conflicting results and wide confidence intervals. Clarification of this issue has implications for the pathogenesis of coronary disease, and for public health efforts to reduce coronary disease in women. RESEARCH DESIGN AND METHODS: We performed a meta-analysis to calculate a summary estimate of the relative risk of coronary death among women with diabetes as compared to those without. For comparison, we also calculated the analogous risk among men. All prospective cohort studies containing both men and women, and both patients with and without diabetes, were examined. Sixteen studies were identified; 10 had sufficient data for statistical analysis. RESULTS: After combining studies that adjusted for other cardiac risk factors, the relative risk of coronary death from diabetes was 2.58 (95% CI 2.05-3.26) for women and 1.85 (1.47-2.33) for men. This difference is statistically significant (P = 0.045). Other sensitivity analyses did not change these estimates appreciably. CONCLUSIONS: The impact of diabetes on the risk of coronary death is significantly greater for women than men. Further research is required to explain this clinically meaningful difference between the sexes.
No major association of breast-feeding, vaccinations, and childhood viral diseases with early islet autoimmunity in the German BABYDIAB Study.
Authors: Hummel M , Füchtenbusch M , Schenker M , Ziegler A G
Published: March 2007

OBJECTIVE: Environmental factors have been suggested to play an important role in the pathogenesis of type 1 diabetes. The aim of this study was to assess the influence of breast-feeding, vaccinations, and childhood viral diseases on the initiation of islet autoimmunity in early childhood. RESEARCH DESIGN AND METHODS: Data were prospectively collected from questionnaires obtained at birth, at 9 months of age, and at 2 years of age in 823 offspring from parents with type 1 diabetes. By 2 years of age, 31 offspring had islet antibodies, and 10 developed overt diabetes by the time of follow-up. RESULTS: In offspring from mothers with type 1 diabetes, duration of exclusive and total breast-feeding did not differ between islet antibody-positive and -negative children, regardless of HLA genotype, and breast-feeding of 3 months or longer was not associated with protection from antibody development or diabetes onset. In offspring from diabetic fathers, non-statistically significant reductions in exclusive and total breast-feeding times were observed in the antibody-positive cohort. Neither type nor quantity of vaccinations (including Bacille Calmette-Guerin vaccine; haemophilus influenzae vaccine; diphtheria, tetanus, and pertussis vaccine; tick-born encephalitis vaccine; or measles, mumps, and rubella vaccine) were associated with the development of islet antibodies and diabetes. Measles, mumps, and rubella were not reported in children with islet antibodies or diabetes. CONCLUSIONS: This study showed no evidence that proposed environmental factors affect islet antibody development in the first 2 years of life in offspring from parents with type 1 diabetes.
Efficacy of troglitazone on body fat distribution in type 2 diabetes.
Authors: Akazawa S , Sun F , Ito M , Kawasaki E , Eguchi K
Published: March 2007

OBJECTIVE: The insulin-sensitizing action of troglitazone may be mediated through the activation of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and the promotion of preadipocyte differentiation in adipose tissue on which troglitazone has depot-specific effects. We investigated the relationship between efficacy of the drug and body fat distribution. Changes in body fat distribution were also investigated by long-term administration of the drug. RESEARCH DESIGN AND METHODS: Troglitazone was given at a dose of 400 mg/day to 20 patients with type 2 diabetes whose diet and sulfonylurea therapy produced unsatisfactory glycemic control (HbA(1c) >7.8%) and whose insulin secretory capacity was found to be preserved (postprandial C-peptide >3 ng/ml). HbA(1c) values, serum lipid levels, and body weight were measured monthly Body fat distribution was evaluated in subcutaneous (SC) and visceral fat using a computed tomography scan at umbilical levels before and after troglitazone therapy RESULTS: During the 1-year troglitazone treatment, HbA(1c) was significantly decreased (from 9.2 +/- 0.2 to 7.1 +/- 0.2%, P < 0.01), showing lowest values at 4-6 months, whereas body weight was significantly increased (BMI 24.6 +/- 0.6 to 25.7 +/- 0.6 kg/m2, P < 0.01). Reduction of HbA(1c) (deltaHbA(1c)) from the baseline value during treatment was significantly greater in obese patients (BMI >26 kg/m2) than in nonobese patients (-3.2 +/- 0.4 vs. -2.1 +/- 0.3%, P < 0.05) and was more significant in women than in men (-3.2 +/- 0.2 vs. - 1.4 +/- 0.2%, P < 0.01). The level of deltaHbA(1c) during treatment showed a significant negative correlation with SC fat area (r = -0.742, P < 0.01) but not with visceral fat area. Weight gain during troglitazone treatment resulted in increased accumulation of SC fat without a change in visceral fat area and, consequently. in a significant decrease in the visceral-to-SC fat ratio. CONCLUSIONS: Predominant accumulation of SC fat for the visceral fat tissue was an important predictor of the efficacy of troglitazone therapy in patients with type 2 diabetes. Greater efficacy of troglitazone was observed in women who were characterized by more accumulation of SC adipose tissue than men. Long-term administration of the drug resulted in weight gain with increased accumulation of SC adipose tissue, probably because of the activation of PPAR-gamma in the region.
Effect of pregnancy on microvascular complications in the diabetes control and complications trial. The Diabetes Control and Complications Trial Research Group.
Authors:   Diabetes Control and Complications Trial Research Group
Published: March 2007

OBJECTIVE: To assess the effect of pregnancy on the development and progression of retinopathy and microalbuminuria in type 1 diabetes. RESEARCH DESIGN AND METHODS: We conducted longitudinal analyses of the Diabetes Control and Complications Trial (DCCT), a multicenter controlled clinical trial that compared intensive treatment with conventional diabetes therapy and studied 180 women who had 270 pregnancies and 500 women who did not become pregnant during an average of 6.5 years of follow-up. Women assigned to the conventional treatment group were changed to intensive therapy if they were planning pregnancy or as soon as possible after conception. Fundus photography was performed every 6 months, and the urinary albumin excretion rate (AER) was measured annually. RESULTS: Compared with nonpregnant women, pregnant women had a 1.63-fold greater risk of any worsening of retinopathy from before to during pregnancy (P < 0.05) in the intensive treatment group; the risk was 2.48-fold greater for pregnant vs. not pregnant women in the conventional group (P < 0.001). In the conventional group, the odds of > or =3-step progression from the baseline retinopathy level was >2.9-fold among pregnant vs. not pregnant women (P = 0.003). The odds ratio (OR) peaked during the second trimester (OR = 4.26, P = 0.001) and persisted as long as 12 months postpregnancy (OR = 2.87, P = 0.005). The level of AER during pregnancy in the intensive group, but not in the conventional group, was significantly elevated from the level at baseline, albeit in the normal range. Although individual patients had transient worsening of retinopathy during pregnancy, even to the proliferative level, at the end of the DCCT, mean levels of retinopathy and albuminuria in subjects who had become pregnant were similar to those in subjects who had not become pregnant within each treatment group. CONCLUSIONS: Pregnancy in type 1 diabetes induces a transient increase in the risk of retinopathy; increased ophthalmologic surveillance is needed during pregnancy and the first year postpartum. The long-term risk of progression of early retinopathy and albumin excretion, however, does not appear to be increased by pregnancy.
Prevalence of diabetes estimated by plasma glucose criteria combined with standardized measurement of HbA1c among health checkup participants on Miyako Island, Japan.
Authors: Takahashi Y , Noda M , Tsugane S , Kuzuya T , Ito C , Kadowaki T
Published: March 2007

OBJECTIVE: To estimate the prevalence of diabetes in participants of an annual health checkup in the district of the Miyako Public Health Center (Okinawa, Japan) by using the revised criteria of the Japan Diabetes Society (JDS). RESEARCH DESIGN AND METHODS: The subjects studied here were all Japanese and 45-75 years of age at the time of the health examination in 1998. Diagnosis of diabetes was based on the following: 1) fasting plasma glucose > or =7.0 mmol/l, 2) casual plasma glucose > or =11.1 mmol/l, 3) HbA(1c) > or =6.1%, and 4) self-report on a special questionnaire given at the examination. The HbA(1c) value was standardized by the measurement of 2 standard samples provided by the JDS. RESULTS: Among the 2,621 subjects, 59.7% had their fasting blood glucose levels measured. Of the subjects diagnosed as having diabetes, 154 (12.6%) were men and 115 (8.6%) women. Among the subjects newly diagnosed with diabetes from their fasting blood glucose levels. 27.5% of the men and 21.9% of the women had diagnoses based on HbA(1c) alone. Overall, 34.9% of the subjects with newly diagnosed diabetes were identified by plasma glucose (PG) alone and 33.0% were diagnosed by HbA(1c) alone. CONCLUSIONS: The combination of PG and HbA(1c) resulted in a considerable increase in newly diagnosed diabetes as compared with the use of only one of these parameters. Considering the convenience and correlation with vascular complications, use of the 2 tests may be beneficial in epidemiological studies of the Japanese population to identify high-risk groups for micro- and macrovascular diseases.
Multicenter evaluation of the Glucometer Elite XL meter, an instrument specifically designed for use with neonates.
Authors: Girouard J , Forest J C , Massé J , Leroux M , Bradburn N C , Noblet T C , Joynes J O , Baum J
Published: March 2007

OBJECTIVE: To evaluate the clinical performance of the Glucometer Elite XL Diabetes Care System in neonatal settings using a multicenter study RESEARCH DESIGN AND METHODS: A total of 388 blood specimens from 333 neonates were included in the study. A capillary or arterial sample was analyzed for determination of glucose with the Glucometer Elite XL system by an attending trained nurse. Through the same sampling site, a specimen was collected and sent to the laboratory for measurement of plasma glucose, bilirubin, and hematocrit. RESULTS: The regression analysis between the results of the Glucometer Elite XL system and comparative methods resulted in the following: Glucometer Elite XL meter = 1.01 x laboratory method + 0.02 mmol/l (n = 388). For the 1.1-4.0 mmol/l plasma glucose range, the regression was Glucometer Elite XL meter = 1.07 x laboratory method + 0.12 mmol/l (n = 150). A difference plot indicated a mean bias of 0.04 mmol/l (95% CI -0.01 to 0.10). No relationship was found between meter glucose biases and hematocrit levels (r = 0.10, P = 0.14). Although a statistically significant correlation existed between bilirubin levels and the glucose meter biases (r = 0.14, P = 0.005), the predicted mean biases were of little clinical significance. CONCLUSIONS: The Glucometer Elite XL system showed a good performance when used in neonatal settings.
Effect of acarbose on insulin sensitivity in elderly patients with diabetes.
Authors: Meneilly G S , Ryan E A , Radziuk J , Lau D C , Yale J F , Morais J , Chiasson J L , Rabasa-Lhoret R , Maheux P , Tessier D , Wolever T , Josse R G , Elahi D
Published: March 2007

OBJECTIVE: To study the effect of acarbose, an alpha-glucosidase inhibitor, on insulin release and insulin sensitivity in elderly patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Elderly patients with type 2 diabetes were randomly treated in a double-blind fashion with placebo (n = 23) or acarbose (n = 22) for 12 months. Before and after randomization, subjects underwent a meal tolerance test and a hyperglycemic glucose clamp study designed to measure insulin release and sensitivity. RESULTS: After 12 months of therapy there was a significant difference in the change in fasting plasma glucose levels (0.2 +/- 0.3 vs. -0.5 +/- 0.2 mmol/l, placebo vs. acarbose group, respectively; P < 0.05) and in incremental postprandial glucose values (-0.4 +/- 0.6 vs. -3.5 +/- 0.6 mmol/l, placebo vs. acarbose group, P < 0.001) between groups. There was a significant difference in the change in HbA(1c) values in response to treatment (0.4 +/- 0.2 vs. -0.4 +/- 0.1%, placebo vs. acarbose group, P < 0.01). The change in fasting insulin in response to treatment (-2 +/- 2 vs. -13 +/- 4 pmol/l, placebo vs. acarbose group, P < 0.05) and incremental postprandial insulin responses (-89 +/- 26 vs. -271 +/- 59 pmol/l, placebo vs. acarbose group, P < 0.01) was also significantly different between groups. During the hyperglycemic clamps, glucose and insulin values were similar in both groups before and after therapy However, there was a significant difference in the change in insulin sensitivity in response to treatment between the placebo and the acarbose groups (0.001 +/- 0.001 vs. 0.004 +/- 0.001 mg/kg x min(-1) [pmol/l](-1), respectively, P < 0.05) CONCLUSIONS: Acarbose increases insulin sensitivity but not insulin release in elderly patients with diabetes.
Nationwide survey of comorbidity, use, and costs of all medications in Finnish diabetic individuals.
Authors: Reunanen A , Kangas T , Martikainen J , Klaukka T
Published: March 2007

OBJECTIVE: To investigate comorbidity and overall use and costs of medication for all Finnish individuals with diabetes treated with drugs compared with sex- and age-matched control subjects. RESEARCH DESIGN AND METHODS: According to a cross-sectional population study using national registries, 116,224 individuals purchased antidiabetic medications in Finland in 1995. The same number of nondiabetic individuals matched for sex, age, and area of residence were chosen as control subjects. Age at onset of diabetes was used as a criterion for distinguishing between type 1 and type 2 diabetes. The criterion could be applied in 74% of cases. A total of 16,955 individuals were defined as having type 1 diabetes, and 68,517 were defined as having type 2 diabetes. Comorbidity was determined by linkage with a national register including all individuals entitled to special reimbursement for drug treatment for a range of chronic diseases. Data on use and costs of all medications prescribed were obtained from drug purchase records. RESULTS: Cardiovascular diseases and uremia were, as expected, the chronic diseases most closely associated with diabetes. Use of almost all kinds of medication was significantly greater in individuals with type 1 and type 2 diabetes than in control subjects. The greatest differences were observed in relation to cardiovascular drugs and antibiotics. Unexpectedly low use of antiasthmatics was observed in individuals with both types of diabetes, low use of neuroleptics was observed in type 1 diabetic individuals, and low use of hormone replacement therapy was observed in women with type 2 diabetes. Total costs of medications for individuals with diabetes were 3.5 times greater than those for nondiabetic control subjects. The higher costs were mostly attributable to insulin therapy for individuals with type 1 diabetes. The higher costs for individuals with type 2 diabetes were related to the cost of medications other than antidiabetic medication. The possible selection bias in omitting diabetic individuals treated with diet only and individuals in whom diabetes type could not be determined must be considered in interpreting the results. CONCLUSIONS: Greater use by and costs of medications for individuals with diabetes than for nondiabetic individuals is related not only to antidiabetic treatment but also to all other kinds of medications. Although drug treatment and the prevalence of several chronic conditions were overall greater in individuals with diabetes versus other individuals, some exceptions merit further study
Outcomes of screening for diabetes in high-risk Hong Kong Chinese subjects.
Authors: Ko G T , Chan J C , Tsang L W , Yeung V T , Chow C C , Cockram C S
Published: March 2007

OBJECTIVE: To examine the significance of individual risk factors on the development of diabetes in subjects who underwent screening for diabetes. RESEARCH DESIGN AND METHODS: A total of 1,649 Chinese subjects underwent screening for diabetes. They were asymptomatic but had known risk factors for diabetes, including a positive family history of diabetes, a past history of gestational diabetes, obesity, hypertension, and/or dyslipidemia. Another 799 age-matched subjects from the community who had no risk factors for diabetes were used as the comparison group. RESULTS: Of the 1,649 subjects who underwent screening, 241 (14.6%) had diabetes. In these subjects, 989 (60.0%) had 1 risk factor, 502 (30.4%) had 2 risk factors, 141 (8.6%) had 3 risk factors, and 17 (1.0%) had 4 or 5 risk factors for diabetes. Of the 799 control subjects, 29 (3.6%) had diabetes. Compared with the comparison group, the odds ratio (95% CI) of having diabetes after adjustment for age was 5.2 (3.5-7.7) in the 1,649 subjects with known risk factors. The odds ratio of having diabetes increased from 3.7 in subjects with 1 risk factor to 28.4 in subjects with 4 or 5 risk factors. CONCLUSIONS: In men, age, BMI, family history of diabetes, and dyslipidemia, and in women, age, BMI, hypertension, dyslipidemia, total cholesterol, and history of gestational diabetes are associated with increased odds of developing diabetes. These risk factors have additive effects on the odds of having diabetes. Early and regular screening for diabetes and other cardiovascular risk factors is essential in these high-risk individuals.
Two years of intensive glycemic control and left ventricular function in the Veterans Affairs Cooperative Study in Type 2 Diabetes Mellitus (VA CSDM).
Authors: Pitale S U , Abraira C , Emanuele N V , McCarren M , Henderson W G , Pacold I , Bushnell D , Colwell J A , Nuttall F Q , Levin S R , Sawin C T , Comstock J P , Silbert C K
Published: March 2007

OBJECTIVE: The Veterans Affairs Cooperative Study in Type 2 Diabetes Mellitus (VA CSDM) was a multicenter randomized prospective study of 153 male type 2 diabetic patients to assess the ability to sustain clinically significant glycemic separation between intensive and standard treatment arms. A trend toward an excess of combined cardiovascular events in the intensive treatment arm of this trial was reported earlier. The present analysis was done to evaluate the effect of 2 years of intensive glycemic control on the left ventricular (LV) function. RESEARCH DESIGN AND METHODS: The patients were randomized to intensive step treatment with insulin alone or with sulfonylurea (intensive treatment arm [INT], n = 75) or to standard once-daily insulin injection (standard treatment arm [STD], n = 78) treatment. A total of 136 patients (standard treatment arm [STD], n = 70; INT, n = 66) had radionuclide ventriculography at entry and at 24 months for the assessment of LV function. RESULTS: There was no difference in the mean LV ejection fraction (at entry: STD 57.1+/-9.51%; INT 58.1+/-8.7%; at 24 months: STD 57.3+/-10.8%, INT 59.5+/-10.7%), peak filling rate (at entry: STD 2.6+/-0.7 end diastolic volume per second, INT 2.4+/-0.8 end diastolic volume per second; at 24 months: STD 2.7+/-1.0 end diastolic volume per second, INT 2.5+/-0.7 end diastolic volume per second), or time to peak filling rate (at entry: STD 195.3+/-69.5 ms, INT 185.6 +/-62.4 ms; at 24 months: STD 182.6+/-64.8 ms, INT 179.2+/-61.2 ms) between the 2 treatment arms. A subgroup analysis of 104 patients (STD, n = 53; INT, n = 51) that omitted individuals with intervening cardiac events/revascularization or a change in cardioactive medications also showed no difference in the LV function at entry and at 24 months between the 2 groups. Abnormal LV ejection fraction at baseline predicted cardiac events (interval between cardiac beats [RR] = 2.5). CONCLUSIONS: Two years of intensive glycemic control does not affect the LV systolic or diastolic function in patients with type 2 diabetes.