bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk Factors for Frequent and Severe Hypoglycemia in Type 1 Diabetes
Authors: Allen Catherine , LeCaire Tamara , Palta Mari , Daniels Kathleen , Meredith Melissa , D’Alessio Donn J. ,   for the Wisconsin Diabetes Registry Project
Published: March 2007

OBJECTIVE—To determine the risk of frequent and severe hypoglycemia and the associated demographic and clinical risk factors.

RESEARCH DESIGN AND METHODS—Demographic and diabetes self-management factors were measured in 415 subjects followed prospectively for 4–6.5 years of type 1 diabetes duration as participants in a population-based incident cohort. Blood samples were collected up to three times yearly to test glycosylated hemoglobin (GHb) levels. Reports of frequent (2–4 times/week) and severe (lost consciousness) hypoglycemia as well as other diabetes self-management data were collected by questionnaires.

RESULTS—Frequent hypoglycemia was common (33 and 35% of participants reported this on the 4- and 6.5-year questionnaires, respectively), whereas severe hypoglycemia occurred much less often. Better glycemic control (odds ratio [OR] 1.3 per 2% decrease in GHb, 95% CI 1.1–1.5) and more frequent self-monitored blood glucose (1.5 per blood glucose check, 1.3–1.7) were independently related to frequent hypoglycemia. The association of frequent hypoglycemia with intensive insulin therapy increased with age. Better glycemic control (1.5 per 2% decrease in GHb, 1.2–2.0) and older age were related to severe hypoglycemic reactions. No sociodemographic factors other than age increased the risk of hypoglycemia.

CONCLUSIONS—Frequent hypoglycemia was common in a population representing the full range of glycemic control in the community. Intensive insulin management and blood glucose monitoring independently predicted frequent but not severe hypoglycemia. This information may be useful for updating patients such that minor changes in diabetes management might decrease the daily burden of this condition while maintaining intensive insulin therapy.
Weighing in on Type 2 Diabetes in the Military
Authors: Paris Robert M. , Bedno Sheryl A. , Krauss Margot R. , Keep Lisa W. , Rubertone Mark V.
Published: March 2007

OBJECTIVES—Current incidence trends in type 2 diabetes portend a significant public health burden and have largely been attributed to similar trends in overweight and physical inactivity. Medical surveillance of the U.S. military indicates that the incidence of all types of diabetes is similar to that in the civilian population (1.9 vs. 1.6 cases per 1,000 person-years) despite weight and fitness standards. Differences in the common determinants of diabetes have not been studied in the military population, which may provide novel clues to the increasing incidence of diabetes in the U.S.

RESEARCH DESIGN AND METHODS—A case-control study, 4-to-1 matched for age, sex, entry date, time in service, and service component (e.g., Army, Navy), was used to describe the association of race/ethnicity, socioeconomic status, and BMI and blood pressure at entry into military service with the subsequent development of type 2 diabetes.

RESULTS—Increased BMI (adjusted odds ratio, 3.0 for the ≥30 kg/m2 vs. ≤20 kg/m2 categories and 2.0 for the 25.0–29.9 kg/m2 category, compared with the reference category), African-American (adjusted odds ratio, 2.0) and Hispanic origin (adjusted odds ratio, 1.6) compared with white race and rank (adjusted odds ratio for junior enlisted versus officers, 4.1) were all associated with type 2 diabetes.

CONCLUSIONS—Individuals with type 2 diabetes in the U.S. military have risk factors similar to the general U.S. population. Because diabetes is a preventable disease, it is of concern that it is occurring in this population of younger and presumably more fit individuals. This has significant implications for the prevention of diabetes in both military and civilian populations.
Fat Consumption and HbA1c Levels
Authors: Harding Anne-Helen , Sargeant Lincoln A. , Welch Ailsa , Oakes Suzy , Luben Robert N. , Bingham Sheila , Day Nicholas E. , Khaw Kay-Tee , Wareham Nicholas J.
Published: March 2007

OBJECTIVE—To describe the relationship between total dietary fat and the pattern of fat intake and HbA1c.

RESEARCH DESIGN AND METHODS—In this cross-sectional study, 2,759 men and 3,464 women (40–78 years of age) without a previous diagnosis of type 2 diabetes were recruited from a population-based sampling frame. Diet was assessed using a self-reported semiquantitative food frequency questionnaire.

RESULTS—The HbA1c level was negatively associated with the polyunsaturated fat–to–saturated fat ratio (P:S ratio) of the diet (β = −0.0338 HbA1c% per SD change in P:S ratio; P < 0.001) and positively associated with the total level of fat intake (β = 0.0620 HbA1c% per SD change in total fat intake; P < 0.001), adjusted for age and total energy intake. The associations remained significant when adjusted for each other and for total energy, protein, age, sex, family history of diabetes, BMI, waist-to-hip ratio, physical activity, and smoking (for P:S ratio, β = −0.0200 HbA1c% per SD change in P:S ratio, P = 0.013; for total fat, β = 0.420% HbA1c% per SD change in total fat intake, P < 0.001). The benefits from a high P:S ratio were attributed to a lower saturated fat intake.

CONCLUSIONS—These findings demonstrate independent associations between HbA1c concentration across the normal range of HbA1c and both total fat intake and the pattern of dietary fat intake. They provide further support to efforts promoting modifications in the intake of dietary fat.
Obese Premenopausal African-American Women With Normal and Impaired Glucose Tolerance Have a Similar Degree of Insulin Resistance but Differ in β-Cell Function
Authors: Sumner Anne E. , Farmer Nicole M. , Cochran Craig S. , Sebring Nancy G. , Vanevski Konstantina , Reynolds James C. , Premkumar Ahalya , Boston Raymond C.
Published: March 2007

OBJECTIVE—To determine whether insulin resistance and secretion differ in obese premenopausal African-American women with and without glucose intolerance.

RESEARCH DESIGN AND METHODS—A total of 63 women underwent oral glucose tolerance tests (OGTTs). A total of 48 women underwent frequently sampled intravenous glucose tolerance tests (FSIGTs). Insulin resistance was determined from the insulin sensitivity index (SI) from the FSIGT. Insulin secretion during the OGTT was determined by (I30 min − I0 min)/(G30 min − G0 min) and during the FSIGT by the acute insulin response to glucose (AIRg). The disposition index, the product of AIRg and SI, was used to determine whether AIRg was adequate to compensate for insulin resistance. Statistical analyses included one-way analysis of variance with Bonferroni corrections for multiple comparisons and regression analyses.

RESULTS—The women were divided into three groups: nonobese glucose tolerant (n = 32), obese glucose tolerant (n = 17), and obese glucose intolerant (n = 14). The BMI of the three groups were 24.8 ± 2.3, 37.8 ± 5.5, and 42.0 ± 7.6 kg/m2 (mean ± SD), respectively (P < 0.0001). The ages of the three groups were 34.9 ± 8.4, 32.1 ± 5.0, and 41.1 ± 6.3 years (P = 0.011). SI was higher in the nonobese women than in the obese glucose-tolerant women (3.99 ± 1.44 vs. 2.66 ± 2.14 l · mU−1 · min−1, P = 0.03). SI was similar in the obese glucose-intolerant and obese glucose-tolerant women (2.12 ± 1.27 vs. 2.66 ± 2.14 l · mU−1 · min−1, P = 0.9). OGTT showed that insulin secretion was lower in the glucose-intolerant than the obese glucose-tolerant women (1.73 ± 1.38 vs. 3.62 ± 2.11, P = 0.005). FSIGT showed that AIRg was not significantly lower in glucose-intolerant than in obese glucose-tolerant women (807 ± 665 vs. 1,253 ± 655 mU · l−1 · min, P = 0.078). The disposition index was lower in glucose-intolerant than in obese glucose-tolerant women (1,324 ± 1,061 vs. 2,656 ± 1,415, P = 0.014).

CONCLUSIONS—Obese premenopausal African-American women with and without glucose intolerance have a similar degree of insulin resistance but differ in insulin secretion.
ACE Gene Polymorphism as a Prognostic Indicator in Patients With Type 2 Diabetes and Established Renal Disease
Authors: Fava Stephen , Azzopardi Joseph , Ellard Sian , Hattersley Andrew T.
Published: March 2007

OBJECTIVE—To investigate whether the DD genotype is a predictor of mortality and of the decline in renal function in patients with type 2 diabetes and established nephropathy.

RESEARCH DESIGN AND METHODS—A total of 56 such patients of Maltese Caucasian descent were recruited, and their ACE genotype was determined. Serum creatinine was estimated approximately every 4 months. The glomerular filtration rate (GFR) was calculated according to the Cockroft-Gault formula, and rate of change was determined by regression analysis.

RESULTS—The rate of change in calculated GFR was −7.76 ml · min–1 · year–1 in those with the DD genotype (n = 31) and −1.17 ml · min–1 · h–1 in those with the ID or II genotype (n = 25) (P < 0.01). The 3-year mortality was 45.2% in the DD group compared with 20.0% in the ID/II group (P < 0.05).

CONCLUSIONS—The DD genotype of the ACE gene polymorphism is associated with a more rapid decline in renal function and higher mortality in type 2 diabetic patients with established nephropathy.
Visceral Fat Is a Major Contributor for Multiple Risk Factor Clustering in Japanese Men With Impaired Glucose Tolerance
Authors: Nagaretani Hiroyuki , Nakamura Tadashi , Funahashi Tohru , Kotani Kazuaki , Miyanaga Minoru , Tokunaga Katsuto , Takahashi Masahiko , Nishizawa Hitoshi , Kishida Ken , Kuriyama Hiroshi , Hotta Kikuko , Yamashita Shizuya , Matsuzawa Yuji
Published: March 2007

OBJECTIVE—The significance of abdominal visceral fat accumulation was evaluated in Japanese men with impaired glucose tolerance (IGT).

RESEARCH DESIGN AND METHODS—The IGT subjects (n = 123) were aged 55 ± 9 years with a BMI of 24 ± 3 kg/m2. The 148 control subjects with normal glucose tolerance (NGT) were matched for age and BMI. IGT and NGT were classified according to the 1985 World Health Organization criteria. Abdominal fat distribution was analyzed by computed tomography at umbilical level. Plasma lipid, glucose, and insulin concentrations and blood pressure (BP) were measured.

RESULTS—In subjects with IGT, the average visceral fat area (VFA) was significantly greater than in subjects with NGT. Fasting insulin, the sum of insulin concentrations during an oral glucose tolerance test, insulin resistance according to a homeostasis model assessment for insulin resistance (HOMA-IR), systolic BP, and serum triglyceride were significantly higher, whereas the ΔI30–0/ΔG30–0 was significantly lower, in subjects with IGT. Subjects with IGT and NGT were then divided into three subgroups according to the number of risk factors they possessed (dyslipidemia, hypertension, neither, or both). In both IGT and NGT subjects, BMI, VFA, subcutaneous fat area, fasting insulin, HOMA-IR, and insulin secretion of the homeostasis model assessment were significantly higher in the double–risk factor subgroup than in the no–risk factor subgroup, and VFA was a potent and independent variable in association with the presence of a double risk factor.

CONCLUSIONS—Visceral fat accumulation is a major contributor for multiple risk factor clustering in Japanese men with IGT and NGT.
Once- and Twice-Daily Dosing With Rosiglitazone Improves Glycemic Control in Patients With Type 2 Diabetes
Authors: Phillips Lawrence S. , Grunberger George , Miller Elizabeth , Patwardhan Rita , Rappaport Elizabeth B. , Salzman Alan ,   the Rosiglitazone Clinical Trials Study Group
Published: March 2007

OBJECTIVE— To determine the efficacy of rosiglitazone compared with placebo in reducing hyperglycemia.

RESEARCH DESIGN AND METHODS— After a 4-week placebo run-in period, 959 patients were randomized to placebo or rosiglitazone (total daily dose 4 or 8 mg) for 26 weeks. The primary measure of efficacy was change in the HbAlc concentration.

RESULTS— Rosiglitazone produced dosage-dependent reductions in HbAlc of 0.8, 0.9, 1.1, and 1.5% in the 4 mg o.d., 2 mg b.i.d., 8 mg o.d., and 4 mg b.i.d. groups, respectively, compared with placebo. Clinically significant decreases from baseline in HbAlc were observed in drug-naive patients at all rosiglitazone doses and in patients previously treated with oral monotherapy at rosiglitazone 8 mg o.d. and 4 mg b.i.d. Clinically significant decreases from baseline in HbAlc were also observed with rosiglitazone 4 mg b.i.d. in patients previously treated with combination oral therapy. Approximately 33% of drug-naive patients treated with rosiglitazone achieved HbAlc ≤7% at study end. The proportions of patients with at least one adverse event were comparable among the rosiglitazone and placebo groups. There was no evidence of hepatotoxicity in any treatment group. There were statistically significant increases in weight and serum lipids in all rosiglitazone treatment groups compared with placebo. For LDL and HDL cholesterol, the observed increase appeared to be dose related.

CONCLUSIONS— Rosiglitazone at total daily doses of 4 and 8 mg significantly improved glycemic control in patients with type 2 diabetes and was well tolerated.
Effect of Metformin on Glucagon-Like Peptide 1 (GLP-1) and Leptin Levels in Obese Nondiabetic Subjects
Authors: Mannucci Edoardo , Ognibene Agostino , Cremasco Francesco , Bardini Gianluca , Mencucci Antonella , Pierazzuoli Enrica , Ciani Silvia , Messeri Gianni , Rotella Carlo M.
Published: March 2007

OBJECTIVE—To evaluate the effects of metformin on glucagon-like peptide 1 (GLP-1) and leptin levels.

RESEARCH DESIGN AND METHODS—A total of 10 obese nondiabetic male patients were studied before and after a 14-day treatment with 2,550 mg/day metformin and were compared with 10 untreated obese control subjects. On days 0 and 15, leptin and GLP-1(7–36)amide/(7–37) levels were assessed before and after an oral glucose load during a euglycemic hyperinsulinemic clamp to avoid the interference of variations of insulinemia and glycemia on GLP-1 and leptin secretion. The effects of metformin on GLP-1(7–36)amide degradation in human plasma and in a buffer solution containing dipeptidyl peptidase IV (DPP-IV) were also studied.

RESULTS—Leptin levels were not affected by the oral glucose load, and they were not modified after metformin treatment. Metformin induced a significant (P < 0.05) increase of GLP-1(7–36)amide/(7–37) at 30 and 60 min after the oral glucose load (63.8 ± 29.0 vs. 50.3 ± 15.6 pmol/l and 75.8 ± 35.4 vs. 46.9 ± 20.0 pmol/l, respectively), without affecting baseline GLP-1 levels. No variations of GLP-1 levels were observed in the control group. In pooled human plasma, metformin (0.1–0.5 μg/ml) significantly inhibited degradation of GLP-1(7–36)amide after a 30-min incubation at 37°C; similar results were obtained in a buffer solution containing DPP-IV.

CONCLUSIONS—Metformin significantly increases GLP-1 levels after an oral glucose load in obese nondiabetic subjects; this effect could be due to an inhibition of GLP-1 degradation.
Vitreous Levels of Vascular Cell Adhesion Molecule and Vascular Endothelial Growth Factor in Patients With Proliferative Diabetic Retinopathy
Authors: Hernández Cristina , Burgos Rosa , Cantón Ana , García-Arumí José , Segura Rosa María , Simó Rafael
Published: March 2007

OBJECTIVE—To evaluate the intravitreous concentration of vascular cell adhesion molecule (VCAM)-1 in diabetic patients with proliferative diabetic retinopathy (PDR) and the relationship of VCAM-1 with vascular endothelial growth factor (VEGF).

RESEARCH DESIGN AND METHODS—Serum and vitreous fluid samples were obtained simultaneously at the onset of vitrectomy from 20 diabetic patients with PDR and 20 nondiabetic control subjects with nonproliferative ocular disease. Both groups were matched by serum levels of VCAM-1 and VEGF. VCAM-1 and VEGF were determined by enzyme-linked immunosorbent assay. Statistics were determined using the Mann-Whitney U test and Spearman’s rank correlation test.

RESULTS—The intravitreous concentration of VCAM-1 was significantly elevated in diabetic patients with PDR compared with control subjects (26 ng/ml [19–118] vs. 22 ng/ml [20–47], P < 0.05). A direct correlation between VCAM-1 and total vitreous proteins was detected in diabetic patients (r = 0.64, P = 0.003), but not in control subjects. After adjusting for total intravitreous proteins, VCAM-1 was significantly lower in diabetic patients with PDR than in control subjects (8.2 ng/ml [4–31.4] vs. 43.1 ng/ml [9.7–100], P < 0.001). Intravitreous VEGF concentrations were higher in patients with PDR than in control subjects in absolute terms (1.34 ng/ml [0.16–6.22] vs. 0.009 ng/ml [0.009–0.044], P < 0.0001) and after correcting for total vitreal proteins (0.33 ng/ml [0.01–2.3] vs. 0.013 ng/ml [0.003–0.035], P = 0.0001). Finally, the vitreous ratio of VCAM-1 to proteins correlated with the vitreous ratio of VEGF to proteins in both diabetic patients (r = 0.74, P = 0.001) and control subjects (r = 0.84, P = 0.005).

CONCLUSIONS—The low proportion of VCAM-1 in relation to total vitreal proteins observed in diabetic patients with PDR suggests that VCAM-1 is quenched by diabetic retina. In addition, the direct correlation detected between VCAM-1 and VEGF suggests that cellular adhesion and neovascularization may be linked processes.
Sulfonylurea Treatment of Type 2 Diabetic Patients Does Not Reduce the Vasodilator Response to Ischemia
Authors: Spallarossa Paolo , Schiavo Mara , Rossettin Pierfranco , Cordone Stefano , Olivotti Luca , Cordera Renzo , Brunelli Claudio
Published: March 2007

OBJECTIVE—Sulfonylureas block the activation of vascular potassium-dependent ATP channels and impair the vasodilating response to ischemia in nondiabetic individuals, but it is not known whether this occurs in type 2 diabetic patients under chronic treatment with these drugs. Glimepiride, a new sulfonylurea, apparently has no cardiovascular interactions. The aim of our study was to compare the effect of the widely used compound glibenclamide, the pancreas-specific glimepiride, and diet treatment alone on brachial artery response to acute forearm ischemia.

RESEARCH DESIGN AND METHODS—Brachial artery examination was performed by a high-resolution ultrasound technique on 20 type 2 diabetic patients aged (mean ± SD) 67 ± 2 years and on 18 nondiabetic patients matched for age, hypertension, and dislipidemia. Diabetic subjects underwent three separate evaluations at the end of each 8-week treatment period, during which they received glibenclamide, glimepiride, or diet alone according to crossover design. Scans were obtained before and after 4.5 min of forearm ischemia. Postischemic vasodilation and hyperemia were expressed as percent variations in vessel diameter and blood flow.

RESULTS—Postischemic vasodilation and hyperemia were, respectively, 5.42 ± 0.90 and 331 ± 38% during glibenclamide, 5.46 ± 0.69 and 326 ± 28% during glimepiride, and 5.17 ± 0.64 and 357 ± 35% during diet treatment (NS). These results were similar to those found in the nondiabetic patients (6.44 ± 0.68 and 406 ± 42%, NS).

CONCLUSIONS—In type 2 diabetic patients, the vasodilating response to forearm ischemia was the same whether patients were treated with diet treatment alone or with glibenclamide or glimepiride at blood glucose–lowering equipotent doses.
Diabetes, Impaired Fasting Glucose, and Elevated HbA1c in U.S. Adolescents: The Third National Health and Nutrition Examination Survey
Authors: Fagot-Campagna Anne , Saaddine Jinan B. , Flegal Katherine M. , Beckles Gloria L.A.
Published: March 2007

OBJECTIVE—Using population-based data, we estimated the prevalence of diabetes, impaired fasting glucose, and elevated HbA1c (>6%) levels in U.S. adolescents.

RESEARCH DESIGN AND METHODS—The Third National Health and Nutrition Examination Survey (1988–1994) examined a representative sample of the U.S. population, which included 2,867 adolescents aged 12–19 years who had serum glucose measured.

RESULTS—A total of 13 adolescents in the sample were considered to have diabetes; 9 reported using insulin, 2 reported using oral agents only, and 2 did not report any treatment but had high glucose levels (≥11.1 mmol/l regardless of length of fast or ≥7.0 mmol/l after an 8-h fast). Four of these cases (31% of the sample with diabetes) were considered to have type 2 diabetes. The estimated prevalence of diabetes (all types) per 100 adolescents ages 12–19 years was 0.41% (95% confidence interval 0–0.86). The prevalence of impaired fasting glucose (≥6.1 mmol/l) among adolescents without diabetes who had fasted for at least 8 h was 1.76% (0.02–3.50). The prevalence of elevated HbA1c (>6%) was 0.39% (0.04–0.74).

CONCLUSIONS—National data reflect the presence of type 2 diabetes in U.S. adolescents, but the survey sample size was not large enough to obtain precise prevalence estimates because of the relatively low prevalence.
Deterioration of the Metabolic Risk Profile in Women
Authors: Pascot Agnés , Després Jean-Pierre , Lemieux Isabelle , Alméras Natalie , Bergeron Jean , Nadeau André , Prud’homme Denis , Tremblay Angelo , Lemieux Simone
Published: March 2007

OBJECTIVE—To determine whether the impaired glucose tolerance (IGT) state contributes to the deterioration of the metabolic profile in women after taking into account the contribution of visceral adipose tissue (AT) accumulation, as measured by computed tomography.

RESEARCH DESIGN AND METHODS—We studied 203 women with normal glucose tolerance (NGT) and 46 women with IGT, defined as a glycemia between 7.8 and 11.1 mmol/l measured 2 h after a 75-g oral glucose load.

RESULTS—Women with IGT were characterized by a higher visceral AT accumulation and by higher concentrations of fasting plasma glucose, insulin, and C-peptide as well as by higher plasma concentrations of cholesterol, triglycerides, and apolipoprotein B (apoB) and by greater cholesterol–to–HDL-cholesterol ratio, reduced LDL peak particle size, lower HDL-cholesterol and HDL2-cholesterol concentrations, and higher blood pressure (P < 0.01) than women with NGT. When we matched 27 pairs of women for visceral AT and fat mass as well as for menopausal status, differences previously found in LDL-cholesterol, LDL peak particle size, HDL-cholesterol, and HDL2-cholesterol concentrations as well as in the cholesterol–to–HDL-cholesterol ratio and blood pressure were eliminated, whereas triglyceride concentrations remained significantly higher in women with IGT.

CONCLUSIONS—A high visceral AT accumulation is a major factor involved in the deterioration of many metabolic variables in women with IGT, with the notable exception of triglyceride concentrations, which remained significantly different between women with NGT and women with IGT after adjustment for visceral fat.
Glycemic Control Is a Predictor of Survival for Diabetic Patients on Hemodialysis
Authors: Morioka Tomoaki , Emoto Masanori , Tabata Tsutomu , Shoji Tetsuo , Tahara Hideki , Kishimoto Hiroshi , Ishimura Eiji , Nishizawa Yoshiki
Published: March 2007

OBJECTIVE—To investigate the impact of glycemic control on the survival of diabetic subjects with end-stage renal disease (ESRD) starting hemodialysis treatment.

RESEARCH DESIGN AND METHODS—This single-center prospective observational study enrolled 150 diabetic ESRD subjects (109 men and 41 women; age at hemodialysis initiation, 60.5 ± 10.2 years) at start of hemodialysis between January 1989 and December 1997. The subjects were divided into groups according to their glycemic control level at inclusion as follows: good HbA1c <7.5%, n = 93 (group G), and poor HbA1c ≥7.5%, n = 57 (group P); and survival was followed until December 1999, with a mean follow-up period of 2.7 years.

RESULTS—Group G had better survival than group P (the control group) (P = 0.008). At inclusion, there was no significant difference in age, sex, systolic blood pressure (SBP), BMI, cardio-to-thoracic ratio (CTR) on chest X-ray, and serum creatinine (Cre) or hemoglobin (Hb) levels between the two groups. After adjustment for age and sex, HbA1c was a significant predictor of survival (hazard ratio 1.133 per 1.0% increment of HbA1c, 95% CI 1.028–1.249, P = 0.012), as were Cre and CTR.

CONCLUSIONS—Good glycemic control (HbA1c <7.5%) predicts better survival of diabetic ESRD patients starting hemodialysis treatment.
Diabetes and the Risk of Infection-Related Mortality in the U.S.
Authors: Bertoni Alain G. , Saydah Sharon , Brancati Frederick L.
Published: March 2007

OBJECTIVE—To determine whether diabetes predicts infection-related mortality and to clarify the extent to which this relationship is mediated by comorbid conditions that may themselves increase risk of infection.

RESEARCH DESIGN AND METHODS—We performed a retrospective cohort study using the Second National Health and Nutrition Examination Survey Mortality Study of 9,208 adults aged 30–74 years in 1976–1980. We defined demographic variables, diabetes, cardiovascular disease (CVD), and smoking by self-report; BMI, blood pressure, and serum cholesterol from baseline examination; and cause-specific mortality from death certificates.

RESULTS—Over 12–16 years of follow-up, 36 infection-related deaths occurred among 533 adults with diabetes vs. 265 deaths in 8,675 adults without diabetes (4.7 vs. 1.5 per 1,000 person-years, P < 0.001). Diabetes (RR 2.0, 95% CI 1.2–3.2) and congestive heart failure (2.8, 1.6–5.1) were independent predictors of infection-related mortality after simultaneous adjustment for age, sex, race, poverty status, smoking, BMI, and hypertension. After subdividing infection-related deaths into those with (n = 145) and without (n = 156) concurrent cardiovascular diagnoses at the time of death, diabetic adults were at risk for infection-related death with CVD (3.0, 1.8–5.0) but not without CVD (1.0, 0.5–2.2).

CONCLUSIONS—These nationally representative data suggest that diabetic adults are at greater risk for infection-related mortality, and the excess risk may be mediated by CVD.
Prevalence of Polycystic Ovary Syndrome Among Premenopausal Women With Type 2 Diabetes
Authors: Peppard Heather R. , Marfori Jennifer , Iuorno Maria J. , Nestler John E.
Published: March 2007

OBJECTIVE—Women with polycystic ovary syndrome (PCOS) have an increased risk for developing type 2 diabetes. Few studies have assessed women with type 2 diabetes to determine the frequency of PCOS in this population.

RESEARCH DESIGN AND METHODS—To determine the prevalence of PCOS among premenopausal women with type 2 diabetes, we conducted a retrospective cross-sectional prevalence study. We reviewed the medical records of all women seen in the Diabetes Clinic of the Medical College of Virginia Hospitals between January 1995 through February 2000. A diagnosis of PCOS was based on 1) oligomenorrhea, 2) hyperandrogenism (biochemical or clinical), and 3) exclusion of other related disorders.

RESULTS—We reviewed the medical records of 618 women with diabetes and identified 47 women eligible for study. Of the 47 women, 30 consented to an evaluation. Of the 30 women evaluated, 8 were identified as having PCOS (6 women reported a previous PCOS diagnosis and 2 women were newly diagnosed), resulting in a prevalence of 26.7%.

CONCLUSIONS—We concluded that PCOS occurs frequently among premenopausal women with type 2 diabetes.
The Synergistic Effect of Miglitol Plus Metformin Combination Therapy in the Treatment of Type 2 Diabetes
Authors: Chiasson Jean-Louis , Naditch Lisa ,   for the Miglitol Canadian University Investigator Group
Published: March 2007

OBJECTIVE—To investigate the efficacy and safety of miglitol in combination with metformin in improving glycemic control in outpatients in whom type 2 diabetes is insufficiently controlled by diet alone.

RESEARCH DESIGN AND METHODS—In this multicenter, double-blind, placebo-controlled study, 324 patients with type 2 diabetes were randomized, after an 8-week placebo run-in period, to treatment with either placebo, miglitol alone, metformin alone, or miglitol plus metformin for 36 weeks. The miglitol was titrated to 100 mg three times a day and metformin was administered at 500 mg three times a day. The primary efficacy criterion was change in HbA1c from baseline to the end of treatment. Secondary parameters included changes in fasting and postprandial plasma glucose and insulin levels, serum triglyceride levels, and responder rate.

RESULTS—A total of 318 patients were valid for intent-to-treat analysis. A reduction in mean placebo-subtracted HbA1c of −1.78% was observed with miglitol plus metformin combination therapy, which was significantly different from treatment with metformin alone (−1.25; P = 0.002). Miglitol plus metformin also resulted in better metabolic control than metformin alone for fasting plasma glucose (−44.8 vs. −20.4 mg/dl; P = 0.0025), 2-h postprandial glucose area under the curve (−59.0 vs. –18.0 mg/dl; P = 0.0001), and responder rate (70.6 vs. 45.52%; P = 0.0014). All therapies were well tolerated.

CONCLUSIONS—In type 2 diabetic patients, miglitol in combination with metformin gives greater glycemic improvement than metformin monotherapy.
Gestational Diabetes Mellitus Diagnosed With a 2-h 75-g Oral Glucose Tolerance Test and Adverse Pregnancy Outcomes
Authors: Schmidt Maria I. , Duncan Bruce B. , Reichelt Angela J. , Branchtein Leandro , Matos Maria C. , Costa e Forti Adriana , Spichler Ethel R. , Pousada Judith M.D.C. , Teixeira Margareth M. , Yamashita Tsuyoshi ,   For the Brazilian Gestational Diabetes Study Group
Published: March 2007

OBJECTIVE—To evaluate American Diabetes Association (ADA) and World Health Organization (WHO) diagnostic criteria for gestational diabetes mellitus (GDM) against pregnancy outcomes.

RESEARCH DESIGN AND METHODS—This cohort study consecutively enrolled Brazilian adult women attending general prenatal clinics. All women were requested to undertake a standardized 2-h 75-g oral glucose tolerance test (OGTT) between their estimated 24th and 28th gestational weeks and were then followed to delivery. New ADA criteria for GDM require two plasma glucose values ≥5.3 mmol/l (fasting), ≥10 mmol/l (1 h), and ≥8.6 mmol/l (2 h). WHO criteria require a plasma glucose ≥7.0 mmol/l (fasting) or ≥7.8 mmol/l (2 h). Individuals with hyperglycemia indicative of diabetes outside of pregnancy were excluded.

RESULTS—Among the 4,977 women studied, 2.4% (95% CI 2.0–2.9) presented with GDM by ADA criteria and 7.2% (6.5–7.9) by WHO criteria. After adjustment for the effects of age, obesity, and other risk factors, GDM by ADA criteria predicted an increased risk of macrosomia (RR 1.29, 95% CI 0.73–2.18), preeclampsia (2.28, 1.22–4.16), and perinatal death (3.10, 1.42–6.47). Similarly, GDM by WHO criteria predicted increased risk for macrosomia (1.45, 1.06–1.95), preeclampsia (1.94, 1.22–3.03), and perinatal death (1.59, 0.86–2.90). Of women positive by WHO criteria, 260 (73%) were negative by ADA criteria. Conversely, 22 (18%) women positive by ADA criteria were negative by WHO criteria.

CONCLUSIONS—GDM based on a 2-h 75-g OGTT defined by either WHO or ADA criteria predicts adverse pregnancy outcomes.
Relationship Between Ethnicity and Glycemic Control, Lipid Profiles, and Blood Pressure During the First 9 Years of Type 2 Diabetes
Authors: Davis Timothy M. E. , Cull Carole A. , Holman Rury R. ,   for the U.K. Prospective Diabetes Study (UKPDS) Group
Published: March 2007

OBJECTIVE—To assess the relationship among self-reported ethnicity, metabolic control, and blood pressure during treatment of type 2 diabetes.

RESEARCH DESIGN AND METHODS—We studied 2,999 newly diagnosed type 2 diabetic patients recruited to the U.K. Prospective Diabetes Study who were randomized to conventional or intensive glucose control policies if their fasting plasma glucose levels remained >6 mmol/l after a dietary run-in. A total of 2,484 patients (83%) were white Caucasian (WC), 265 patients (9%) were Afro-Caribbean (AC), and 250 patients (8%) were Asian of Indian origin (IA). Variables were assessed at 3, 6, and 9 years.

RESULTS—During the 9-year study period, body weight increased more in WC patients (mean 5.0 kg) than in AC (3.0 kg) and IA (2.5 kg) patients (P < 0.001). After adjusting for age, sex, baseline value, treatment allocation, and change in weight, there were no consistent ethnic differences in mean change in fasting plasma glucose or HbA1c. After adjustment for antihypertensive therapy, increase in systolic blood pressure at 9 years was greatest in AC patients (7 mmHg; P < 0.01 vs. WC patients). Mean diastolic blood pressure, total cholesterol, and LDL cholesterol decreased progressively during the 9 years in each group. In AC patients, the mean increase in HDL cholesterol (0.16 mmol/l) at 3 years, maintained to 9 years, and the mean decrease in plasma triglyceride level (0.4 mmol/l) at 9 years were greater than in WC and IA patients (P < 0.001).

CONCLUSIONS—This study shows important ethnic differences in body weight, lipid profiles, and blood pressure, but not glycemic control, during 9 years after diagnosis of type 2 diabetes. AC patients maintained the most favorable lipid profiles, but hypertension developed in more AC patients than WC or IA patients. Ethnicity-specific glycemic control of type 2 diabetes seems unnecessary, but other risk factors need to be addressed independently.
Randomized Dose Ranging Study of the Reduction of Fasting and Postprandial Glucose in Type 2 Diabetes by Nateglinide (A-4166)
Authors: Gribble Fiona M. , Manley Susan E. , Levy Jonathan C.
Published: March 2007

OBJECTIVE—This randomized crossover double-blind placebo-controlled study aimed to assess the efficacy of nateglinide (A-4166), a novel phenylalanine-derived insulin secretagogue, in type 2 diabetic subjects while fasting and 5 min before a standard meal.

RESEARCH DESIGN AND METHODS—A single dose of nateglinide (60, 120, or 180 mg) or placebo was given to eight diet-treated overnight-fasted type 2 diabetic patients and to seven patients 5 min before a standard breakfast. Plasma glucose, radioimmunoassay insulin, and nateglinide were measured at baseline and for a further 180 min.

RESULTS—The time-averaged 180-min postdose mean decrease in fasting plasma glucose concentration was greater after nateglinide (1.8 mmol/l; 95% CI 1.5–2.0) than after placebo (0.7 mmol/l; 95% CI 0.3–1.2) (P < 0.001). Hypoglycemia did not develop in any of the subjects. Insulin concentrations increased 1.5-, 1.8-, and 1.9-fold with the 60-, 120-, and 180-mg doses, respectively (P < 0.001), peaking ∼30 min after the dose. Nateglinide concentrations peaked after ∼30 min, decreasing to 21% of peak by 180 min. In the meal test, the mean increase (2.9 mmol/l, 2.3–3.6) in plasma glucose over 180 min after placebo was reduced by 1.8 mmol/l (P < 0.001) with the two higher doses of nateglinide.

CONCLUSIONS—A single dose of nateglinide administered to diet-treated type 2 diabetic patients with fasting hyperglycemia increased insulin secretion and reduced fasting glucose without hypoglycemia. Administered 5 min before a meal, nateglinide reduced the postprandial glucose excursion by 64%. With its rapid onset and short duration of action, nateglinide is a promising oral prandial therapy in type 2 diabetes.
Amniotic Fluid Insulin at 14–20 Weeks’ Gestation
Authors: Carpenter Marshall W. , Canick Jacob A. , Hogan Joseph W. , Shellum Curtis , Somers Margaret , Star Jami A.
Published: March 2007

OBJECTIVE—To examine the hypothesis that early second trimester amniotic fluid (AF) insulin concentration is elevated and later fetal growth is augmented in gravidas demonstrating later oral glucose intolerance.

RESEARCH DESIGN AND METHODS—In this prospective observational cohort study, AF was sampled at 14–20 weeks’ gestation in 247 subjects, and 1-h 50-g oral glucose challenge tests (GCTs) were performed at ≥24 weeks. AF insulin was assayed by an automated immuno-chemiluminometric assay (8). Macrosomia was defined as birth weight above the 90th centile.

RESULTS—AF insulin concentration (range 1.4–44.5 pmol/l) correlated positively with gestational age and maternal weight. A logistic regression analysis, adjusted for maternal age and midpregnancy weight, showed increased AF insulin multiples of gestational age-specific medians to be associated with subsequently diagnosed gestational diabetes mellitus (GDM) (OR 1.9, CI 1.3–2.4, P = 0.029). Among 60 subjects with GCT values >7.2 mmol/l, each unit increase in AF insulin multiple of median (MOM) was associated with a threefold increase in fetal macrosomia incidence (3.1, 1.3–4.9, P = 0.048).

CONCLUSIONS—An elevated AF insulin concentration at 14–20 weeks’ gestation is associated with subsequently documented maternal glucose intolerance. Among gravidas with GCT values >7.2 mmol/l, elevated early AF insulin concentration is associated with fetal macrosomia. Maternal glucose intolerance may affect fetal insulin production before 20 weeks’ gestation.
Plantar Tissue Thickness Is Related to Peak Plantar Pressure in the High-Risk Diabetic Foot
Authors: Abouaesha Frag , van Schie Carine H.M. , Griffths Gareth D. , Young Robert J. , Boulton Andrew J.M.
Published: March 2007

OBJECTIVE—To investigate the relationship among plantar foot pressure, plantar subcutaneous tissue thickness, severity of neuropathy (vibration perception threshold [VPT]), callus, and BMI in a large group of neuropathic diabetic patients at risk of foot ulceration.

RESEARCH DESIGN AND METHODS—A total of 157 diabetic neuropathic patients (VPT >25 V) without either peripheral vascular or ulcer history were studied. Plantar foot pressure and plantar tissue thickness were measured at each metatarsal head (MTH) using an optical pedobarograph and an ultrasound scanning platform, respectively.

RESULTS—A significant association was observed between peak plantar pressure and plantar tissue thickness at all MTHs (−0.26 < r < −0.61, P < 0.0001), with the least pronounced association at the first MTH. In addition, the pressure time integral was significantly associated with plantar tissue thickness (−0.24 < r < −0.57, P < 0.0001). BMI was significantly related to plantar tissue thickness (0.18 < r < 0.45, P < 0.05), but not to peak forefoot pressures. Subjects with callus had significantly reduced plantar tissue thickness at all MTHs except the first MTH and increased peak pressures at all MTHs (P < 0.001).

CONCLUSIONS—This study confirms a strong inverse relationship between plantar tissue thickness and dynamic foot pressure measurements. Long-term follow-up of this patient population will confirm whether reduced plantar tissue thickness predicts the development of diabetic foot ulcers.
Long-Term Effectiveness of a Quality Improvement Program for Patients With Type 2 Diabetes in General Practice
Authors: Renders Carry M. , Valk Gerlof D. , Franse Lonneke V. , Schellevis François G. , van Eijk Jacques Th.M. , van der Wal Gerrit
Published: March 2007

OBJECTIVE—To assess the long-term effectiveness of a quality improvement program on care provided and patient outcomes in patients with diabetes.

RESEARCH DESIGN AND METHODS—A nonrandomized trial was performed with 312 patients with type 2 diabetes in the intervention group and 77 patients with type 2 diabetes in the reference group. The follow-up period was 42 months. The quality improvement program focused on improving both the provision of diabetes care and the patient outcomes. The program consisted of clinical practice guidelines, postgraduate education, audit and feedback, templates to register diabetes care, and a recall system. Data on the care provided were abstracted from medical records. Main outcomes on the provision of care were annual number of patient visits, blood pressure, and HbA1c and blood lipid levels. Main patient outcomes were blood pressure and HbA1c and blood lipid levels. Multilevel analysis was used to adjust for dependency between repeated observations within one patient and for clustering of patients within general practices.

RESULTS—Patients in the intervention group received care far more in accordance with the guidelines than patients in the reference group. Odds ratios ranged from 2.43 (95% CI 1.01–5.82) for the measurement of urine albumin to 12.08 (4.70–31.01) for the measurement of blood pressure. No beneficial effect was found on any patient outcome.

CONCLUSIONS—The quality improvement program improved the provision of diabetes care, but this was not accompanied by any effect on patient outcomes.
Utilization of Oral Hypoglycemic Agents in a Drug-Insured U.S. Population
Authors: Boccuzzi Stephen J. , Wogen Jenifer , Fox James , Sung Jennifer C.Y. , Shah Amishi B. , Kim Jennifer
Published: March 2007

OBJECTIVE—Clinical trials provide information regarding the safety and efficacy of medications used to manage type 2 diabetes but do not elucidate drug effectiveness in a typical managed care environment. The aim of this study was to characterize “real-world” drug utilization patterns from both a prescriber and a patient perspective.

RESEARCH DESIGN AND METHODS—We conducted a retrospective analysis of a large administrative pharmacy claims database, using data on continuously pharmacy benefit–eligible members prescribed oral hypoglycemic agents (OHAs).

RESULTS—The 12-month persistence rate for the OHA cohort was low, ranging from 31% for α-glucosidase inhibitors to 60% for metformin; compliance rates varied between 70 and 80%. During the first 12 months of therapy, 36% of the patients remaining on therapy at 12 months had one or more therapy modifications. The mean number of therapy changes increased with the length of patient follow-up, with more than half of all patients experiencing at least one therapy change over the duration of follow-up.

CONCLUSIONS—These findings document the wide variation in utilization patterns associated with pharmacological management of type 2 diabetes, suggesting that opportunity exists to optimize its pharmacological management.
Relations Between ACE Gene and ecNOS Gene Polymorphisms and Resistive Index in Type 2 Diabetic Patients With Nephropathy
Authors: Taniwaki Hiromichi , Ishimura Eiji , Matsumoto Naoki , Emoto Masanori , Inaba Masaaki , Nishizawa Yoshiki
Published: March 2007

OBJECTIVE—ACE and endothelial cell nitric oxide synthase (ecNOS) genotypes have been reported to be related to the incidence of renal diseases and coronary artery diseases. In order to assess the effect of the gene polymorphism of both ACE and ecNOS on renal hemodynamic abnormality, we examined 155 Japanese patients with type 2 diabetes with various stages of nephropathy.

RESEARCH DESIGN AND METHODS—The patients ranged in age from 40 to 72 years (92 men and 63 women). They were divided into four groups: group 1 consisted of patients with urinary albumin excretion (UAE) <30 mg/day (n = 69), group 2 had 30 ≤ UAE < 300 mg/day (n = 44), group 3 had UAE ≥300 mg/day and serum creatinine <1.5 mg/dl (n = 22), and group 4 had serum creatinine >1.5 mg/dl (n = 20). Intrarenal hemodynamics were studied by duplex Doppler sonography in patients with type 2 diabetes. The ACE and ecNOS gene polymorphisms were examined by polymerase chain reaction.

RESULTS—There were no significant differences in sex, BMI, and blood glucose level, but there were differences in HbA1c and lipoprotein profiles among the four groups. There were no significant differences in the distribution of ACE genotype or in the frequency of the ecNOS 4a allele among the four groups. Resistive index (RI) values of the interlobar arteries of group 4 were significantly higher than those of groups 1, 2, and 3, whereas the RI values were not significantly different among groups 1, 2, and 3. Multiple regression analysis showed that age, duration of diabetes, systolic and diastolic blood pressure, and creatinine clearance were significantly associated with the increased RI values, but that there was no significant association between RI values and the ecNOS genotype (R2 = 0.613, P < 0.0001).

CONCLUSIONS—These results suggest that intrarenal hemodynamic abnormalities are present as a feature of the progression of nephropathy in type 2 diabetes, and that they are associated with age, duration of diabetes, decreased creatinine clearance, and blood pressure, but not with the genetic factors of the ACE and ecNOS gene polymorphism in nephropathy of type 2 diabetes.
Endothelial Perturbation in Children and Adolescents With Type 1 Diabetes
Authors: Romano Mario , Pomilio Mariapina , Vigneri Sergio , Falco Angela , Chiesa Pierluigi Lelli , Chiarelli Francesco , Davì Giovanni
Published: March 2007

OBJECTIVE—The progression of diabetic angiopathy is, in most cases, unpredictable. The aim of this study was to investigate early events that could influence the development of diabetic angiopathy.

RESEARCH DESIGN AND METHODS—Circulating levels of von Willebrand factor (vWF) and tissue-plasminogen activator (tPA), defining endothelial perturbation, were measured in 40 young patients with type 1 diabetes. Patients were divided into two groups according to the duration of diabetes (group A, <1 year; group B, >1 year) and compared with a control group of age- and sex-matched healthy individuals. Prothrombin fragment 1 and 2 (F1+2), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) levels were also determined as markers of a prothrombotic state and inflammatory response. A total of 16 of the 20 children in group A were re-examined after 12 months.

RESULTS—Compared with either normal subjects or patients in group B, children in group A showed increased levels of vWF, tPA, F1+2, TNF-α, and CRP. Significant direct correlations between TNF-α or CRP and either vWF, tPA, or F1+2 were observed. Endothelial perturbation was shown in 70% of group A and 20% of group B. After 1 year, 16 of the 20 patients in group A showed a significant reduction in vWF, tPA, F1+2, TNF-α, and CRP levels, whereas endothelial perturbation was reversed in 5 of these patients.

CONCLUSIONS—Endothelial perturbation represents an early and, in some cases, reversible event in the chronology of type 1 diabetes in children. A correlation might exist between the initial inflammatory reaction and the appearance of endothelial perturbation.
C-Reactive Protein in Type 1 Diabetes and Its Relationship to Coronary Artery Calcification
Authors: Colhoun Helen M. , Schalkwijk Casper , Rubens Michael B. , Stehouwer Coen D.A.
Published: March 2007

OBJECTIVE—In 196 type 1 diabetic subjects and 195 nondiabetic subjects aged 30–55 years, we examined whether C-reactive protein (CRP) is elevated in diabetes and whether CRP is associated with coronary artery calcification (CAC).

RESEARCH DESIGN AND METHODS—CRP was measured with a highly sensitive immunoassay. CAC was measured using electron beam computed tomography.

RESULTS—CRP was elevated in diabetic women compared with nondiabetic women (median 1.62 vs. 0.85 mg/l, P < 0.001) independently of other factors, but was similar in diabetic and nondiabetic men (median 0.82 vs. 0.81 mg/l). Insulin dose per day was positively correlated with CRP in diabetic women (Spearman’s ρ = 0.36, P = 0.0003) but much less so in men (ρ = 0.16, P = 0.09). Being in the top tertile for CRP was associated with CAC in diabetic and nondiabetic men even after adjustment for other risk factors (adjusted odds ratio [OR] = 4.6 and 4.3, respectively, P = 0.02 for both). In nondiabetic women, being in the top tertile for CRP was associated with CAC (OR 3.1, P = 0.04), but not independently of BMI (OR = 1 after adjustment). Among diabetic women the association was not significant even before adjustment for BMI (OR = 2.6, P = 0.07).

CONCLUSIONS—Elevated CRP in diabetic women might reflect a particular sensitivity to insulin levels or might reflect insulin resistance. In general, CRP is an important marker of subclinical atherosclerosis, but the clinical significance of elevated CRP in diabetic women needs to be addressed in prospective studies, since CRP was not clearly associated with CAC in this group.