bluuebunny/crossref_metadata_2025 huggingface dataset:
Utility of Casual Postprandial Glucose Levels in Type 2 Diabetes Management
Authors: El-Kebbi Imad M. , Ziemer David C. , Cook Curtiss B. , Gallina Daniel L. , Barnes Catherine S. , Phillips Lawrence S.
Published: March 2007

OBJECTIVE—Because readily available glycemic indicators are needed to guide clinical decision-making for intensification of diabetes therapy, our goals were to define the relationship between casual postprandial plasma glucose (cPPG) levels and HbA1c in patients with type 2 diabetes and to determine the predictive characteristics of a convenient glucose cutoff.

RESEARCH DESIGN AND METHODS—We examined the relationship between cPPG levels (1–4 h post meal) and HbA1c levels in 1,827 unique patients who had both determinations during a single office visit.

RESULTS—The population studied was predominantly African American and middle-aged, with average cPPG of 201 mg/dl and HbA1c of 8.4%. The prevalence of HbA1c ≥7.0% was 67% and HbA1c >6.5% was 77%. Overall, cPPG and HbA1c were linearly correlated (r = 0.63, P < 0.001). The correlation between cPPG and HbA1c was strongest in patients treated with diet alone (n = 348, r = 0.75, P < 0.001) and weaker but still highly significant for patients treated with oral agents (n = 610, r = 0.64, P < 0.001) or insulin (n = 869, r = 0.56, P < 0.001). A cutoff cPPG >150 mg/dl predicted an HbA1c level ≥7.0% in the whole group, with a sensitivity of 78%, a specificity of 62%, and an 80% positive predictive value. The same cPPG cutoff of 150 mg/dl predicted an HbA1c level >6.5%, with a sensitivity of 74%, a specificity of 66%, and an 88% positive predictive value.

CONCLUSIONS—When rapid-turnaround HbA1c determinations are not available, a single cPPG level >150 mg/dl may be used during a clinic visit to identify most inadequately controlled patients and allow timely intensification of therapy.
Left Ventricular Mass Increases With Deteriorating Glucose Tolerance, Especially in Women: Independence of Increased Arterial Stiffness or Decreased Flow-Mediated Dilation
Authors: Henry Ronald M.A. , Kamp Otto , Kostense Piet J. , Spijkerman Annemieke M.W. , Dekker Jacqueline M. , van Eijck Rosemarie , Nijpels Giel , Heine Robert J. , Bouter Lex M. , Stehouwer Coen D.A.
Published: March 2007

OBJECTIVE—Type 2 diabetes and impaired glucose metabolism (IGM) are associated with an increased cardiovascular disease (CVD) risk. Increased left ventricular mass (LVM) is thought to increase CVD risk through several unfavorable cardiac changes. Type 2 diabetes and IGM are associated with increased LVM, but the underlying mechanism is unclear. We investigated the association between glucose tolerance status (GTS) and LVM and explored whether any such association could be mediated through increased arterial stiffness, impaired endothelial function, or the presence of atherosclerosis.

RESEARCH DESIGN AND METHODS—We used ultrasound to measure LVM, carotid and femoral stiffness, carotid-femoral transit time, and flow-mediated vasodilation (FMD) and tonometry to estimate compliance and augmentation index. The study population (n = 780) consisted of 287 individuals with normal glucose metabolism (NGM), 179 with IGM, and 314 with type 2 diabetes, and the mean age was 68.4 years.

RESULTS—In women, after adjusting for age, height, BMI, and mean arterial pressure, LVM increased significantly with deteriorating GTS (LVM 157 g in NGM, 155 g in IGM, and 169 g in type 2 diabetes; P for trend <0.018). Additional adjustment for arterial stiffness, FMD, or the presence of atherosclerosis did not materially alter the results, even though these variables were significantly associated with both GTS and LVM. Indexes of hyperglycemia/-insulinemia or insulin resistance explained at most 7% of the association between GTS and LVM. In men, no statistically significant associations were observed.

CONCLUSIONS—Our data expand the conceptual view of the pathogenesis of GTS-related changes in LVM because we show that the increase in LVM in women is independent of increased arterial stiffness, impaired FMD, or the presence of atherosclerosis. In addition, we show that this increase in LVM is only minimally explained by indexes of hyperglycemia/-insulinemia or insulin resistance. Our data may, in part, explain the increased CVD risk seen in women with deteriorating GTS.
Impact of Iron Deficiency Anemia on Prevalence of Gestational Diabetes Mellitus
Authors: Lao Terence T. , Ho Lai-Fong
Published: March 2007

OBJECTIVE—Increased Hb and ferritin have been associated with gestational diabetes mellitus (GDM). This study was performed to determine whether the prevalence of GDM is influenced by iron deficiency anemia.

RESEARCH DESIGN AND METHODS—In a retrospective case-control study, 242 women with iron deficiency anemia (Hb <10 g/dl with features of iron deficiency) were compared with 484 nonanemic women matched for year of birth, who were delivered within the same 24-month period in our hospital, with respect to maternal demographics, infant outcome, and the prevalence of GDM diagnosed according to the World Health Organization criteria.

RESULTS—There was no difference in the prepregnancy weight or BMI, but the anemic group had more multiparas and significantly lower gestational weight and BMI increments and prevalence of GDM (odds ratio [OR] 0.52, 95% CI 0.27–0.97), which was inversely correlated (P = 0.045) with the duration of anemia. To determine the independent effect of anemia on GDM, multiple logistic regression analysis was performed adjusting for the effects of multiparity and BMI, and anemia was confirmed to be significantly associated with decreased prevalence of GDM (adjusted OR 0.46, 95% CI 0.23–0.90).

CONCLUSIONS—The prevalence of GDM is reduced in iron deficiency anemia, which probably served as a surrogate for other factors such as nutritional inadequacy and reduced gestational weight gain. Further studies on the relationship between nutritional improvement and the increasing prevalence of GDM in the developing world are warranted.
Diabetes Care in an Australian Population
Authors: Tapp Robyn J. , Zimmet Paul Z. , Harper C. Alex , de Courten Maximilian P. , Balkau Beverley , McCarty Daniel J. , Taylor Hugh R. , Welborn Timothy A. , Shaw Jonathan E. ,   on behalf of the Australian Diabetes Obesity and Lifestyle Study Group
Published: March 2007

OBJECTIVE—The aim of this work was to study the frequency of examining for diabetic eye and foot complications in an Australian population and to study factors associated with regular screening.

RESEARCH DESIGN AND METHODS—The Australian Diabetes, Obesity, and Lifestyle Study (AusDiab) was a population-based study of 11,247 people from randomly selected areas of Australia. Participants identified as having previously diagnosed diabetes (n = 475) were invited to participate in the complications study. Measures included foot examination, retinopathy photography, and self-report use of health care services.

RESULTS—Seventy-seven percent of participants reported having an eye examination within the previous 2 years, and 50% reported having their feet examined by a health professional in the previous year. Type of diabetes treatment (odds ratio 1.46, 95% CI 0.85–2.50 for tablets versus diet alone and 4.17, 1.71–10.17 for insulin or insulin and tablets versus diet alone) and visiting a diabetes nurse educator in the previous 12 months (2.14, 1.18–3.87) were independent predictors of having had an eye examination. Duration of diabetes (1.33, 1.06–1.67 per year) and visiting a diabetes nurse educator in the previous 12 months (1.89, 1.20–2.95) were independent predictors of a foot examination.

CONCLUSIONS—This study has shown that retinopathy screening is performed more frequently than foot screening in Australia. This may be due to the implementation of eye screening programs and awareness campaigns. Foot screening appears to be poor, with less than one-half of the population reporting a regular examination for foot complications. In Australia, diabetes nurse educators play a key role in promoting screening for diabetes complications.
Explanations of Socioeconomic Differences in Excess Risk of Type 2 Diabetes in Swedish Men and Women
Authors: Agardh Emilie E. , Ahlbom Anders , Andersson Tomas , Efendic Suad , Grill Valdemar , Hallqvist Johan , Östenson Claes-Göran
Published: March 2007

OBJECTIVE—We investigated to what extent socioeconomic differences in type 2 diabetes risk could be explained by established risk factors (obesity, physical inactivity, smoking, and heredity) and psychosocial factors (low decision latitude at work and low sense of coherence).

RESEARCH DESIGN AND METHODS—This cross-sectional study comprised 3,128 healthy Swedish men and 4,821 women, aged 35–56 years, living in the Stockholm area. An oral glucose tolerance test identified 55 men and 52 women with type 2 diabetes. The relative contribution of established and psychosocial factors to socioeconomic differences in diabetes risk was assessed by comparing analyses with adjustment for different sets of these factors.

RESULTS—The relative risks (RRs) for type 2 diabetes in middle and low socioeconomic groups in men were 2.4 (95% CI 1.0–5.3) and 2.9 (1.5–5.7), respectively, and in women 3.2 (1.5–6.6) and 2.7 (1.3–5.9), respectively. In men, the RRs decreased to 1.9 (0.8–4.4) and 2.1 (1.0–4.2) after adjustment for established risk factors; no further change was found when psychosocial factors were included. In women, the RRs changed to 2.4 (1.1–5.2) and 1.6 (0.7–3.8) by including established risk factors and to 2.3 (1.0–5.1) and 1.9 (0.8–4.3) by inclusion of psychosocial factors. After adjustment for both established and psychosocial factors, the RRs were 1.4 (0.6–3.6) and 1.0 (0.4–2.5), respectively.

CONCLUSIONS—In men, the excess risk of type 2 diabetes was partly explained by established risk factors (36–42%), whereas psychosocial factors had no effect. In women, most of the socioeconomic differences in type 2 diabetes were explained by simultaneous adjustment for established risk factors and psychosocial factors (81–100%).
Early Glycemic Control, Age at Onset, and Development of Microvascular Complications in Childhood-Onset Type 1 Diabetes
Authors: Svensson Maria , Eriksson Jan W. , Dahlquist Gisela
Published: March 2007

OBJECTIVE—The aim of this work was to study the impact of glycemic control (HbA1c) early in disease and age at onset on the occurrence of incipient diabetic nephropathy (MA) and background retinopathy (RP) in childhood-onset type 1 diabetes.

RESEARCH DESIGN AND METHODS—All children, diagnosed at 0–14 years in a geographically defined area in northern Sweden between 1981 and 1992, were identified using the Swedish Childhood Diabetes Registry. From 1981, a nationwide childhood diabetes care program was implemented recommending intensified insulin treatment. HbA1c and urinary albumin excretion were analyzed, and fundus photography was performed regularly. Retrospective data on all 94 patients were retrieved from medical records and laboratory reports.

RESULTS—During the follow-up period, with a mean duration of 12 ± 4 years (range 5–19), 17 patients (18%) developed MA, 45 patients (48%) developed RP, and 52% had either or both complications. A Cox proportional hazard regression, modeling duration to occurrence of MA or RP, showed that glycemic control (reflected by mean HbA1c) during the follow-up was significantly associated with both MA and RP when adjusted for sex, birth weight, age at onset, and tobacco use as potential confounders. Mean HbA1c during the first 5 years of diabetes was a near-significant determinant for development of MA (hazard ratio 1.41, P = 0.083) and a significant determinant of RP (1.32, P = 0.036). The age at onset of diabetes significantly influenced the risk of developing RP (1.11, P = 0.021). Thus, in a Kaplan-Meier analysis, onset of diabetes before the age of 5 years, compared with the age-groups 5–11 and >11 years, showed a longer time to occurrence of RP (P = 0.015), but no clear tendency was seen for MA, perhaps due to lower statistical power.

CONCLUSIONS—Despite modern insulin treatment, >50% of patients with childhood-onset type 1 diabetes developed detectable diabetes complications after ∼12 years of diabetes. Inadequate glycemic control, also during the first 5 years of diabetes, seems to accelerate time to occurrence, whereas a young age at onset of diabetes seems to prolong the time to development of microvascular complications.
Meta-Analysis of the Effect of Diabetes on Restenosis Rates Among Patients Receiving Coronary Angioplasty Stenting
Authors: Gilbert Jeremy , Raboud Janet , Zinman Bernard
Published: March 2007

OBJECTIVE—Coronary artery disease is a significant source of morbidity and mortality in patients with diabetes. Angioplasty has been associated with higher rates of restenosis in patients with diabetes. Numerous studies have been performed to determine whether coronary artery stenting would be useful in decreasing rates of restenosis of coronary vessels in patients with diabetes. This meta-analysis was conducted to determine the effect of diabetes on angiographic restenosis in patients undergoing coronary stenting.

RESEARCH DESIGN AND METHODS—Six studies were included comprising 6,236 individuals—1,166 with diabetes and 5,070 without. The relationships between restenosis rates and age, the percentage of the study population that was male, and the percentage of the study population receiving insulin therapy were examined.

RESULTS—The average restenosis rates among patients with and without diabetes were 36.7 and 25.9%, respectively. Restenosis rates were higher among older populations and populations in which a greater percentage of patients with diabetes were treated with insulin, but they did not vary according to the percentage of men in the studies. The odds ratio of coronary artery restenosis associated with diabetes was 1.61 (95% CI 1.21–2.14, P = 0.004) in univariate logistic regression models, but decreased to 1.30 (0.99–1.70, P = 0.055) after controlling for age in multivariate models, suggesting that the higher restenosis rates found in patients with diabetes can in good part be explained by the older ages of patients with diabetes in these studies.

CONCLUSIONS—Although diabetes is a risk factor for restenosis after coronary angioplasty stenting, the apparent effect of diabetes on restenosis rates in the published literature is overstated and was reduced in this meta-analysis by approximately half after adjusting for differences in age.
Reduced Coronary Artery and Abdominal Aortic Calcification in Hispanics With Type 2 Diabetes
Authors: Reaven Peter D. , Sacks Jerome ,   Investigators for the Veterans Affairs Cooperative Study of Glycemic Control and Complications in Diabetes Mellitus Type 2
Published: March 2007

OBJECTIVE—To compare lifestyle factors, cardiovascular risk factors, and coronary artery calcium (CAC) and abdominal aortic calcium (AAC) levels in Hispanic and non-Hispanic white (NHW) individuals with type 2 diabetes.

RESEARCH DESIGN AND METHODS—We recently demonstrated in a small group of nonreferred, healthy, nondiabetic subjects that CAC was reduced in Hispanics compared with NHWs, despite a worse cardiovascular risk factor profile. In this study, we evaluated whether this ethnic disparity in vascular calcification was present in individuals with type 2 diabetes and in several different arterial beds. Hispanic and NHW subjects (n = 245) with type 2 diabetes were evaluated for cardiovascular risk factors using questionnaires and assays of plasma biomarkers. CAC and AAC were measured by electron-beam computer-assisted tomography.

RESULTS—Although Hispanics were slightly younger than NHWs, other standard risk factors and novel cardiovascular risk factors, including plasminogen activator-1 and fibrinogen levels, were similar between the groups. Despite the similar risk factor profile, the prevalence of cardiovascular disease (CVD) and mean and median levels of CAC and AAC were lower in Hispanics. Furthermore, the distribution of these calcium scores differed from that of NHWs (P < 0.05), with significantly fewer Hispanic subjects having high CAC or AAC scores. These differences were not explained by differences in CVD prevalence or any measured lifestyle or risk factor.

CONCLUSIONS—Hispanics with type 2 diabetes have reduced CAC and AAC levels compared with NHW subjects, suggesting a reduction in the overall burden of vascular calcification and atherosclerosis. These data are consistent with the notion that Hispanics are protected against the development of CVD.
A Systematic Review of Adherence With Medications for Diabetes
Authors: Cramer Joyce A.
Published: March 2007

OBJECTIVE—The purpose of this study was to determine the extent to which patients omit doses of medications prescribed for diabetes.

RESEARCH DESIGN AND METHODS—A literature search (1966–2003) was performed to identify reports with quantitative data on adherence with oral hypoglycemic agents (OHAs) and insulin and correlations between adherence rates and glycemic control. Adequate documentation of adherence was found in 15 retrospective studies of OHA prescription refill rates, 5 prospective electronic monitoring OHA studies, and 3 retrospective insulin studies.

RESULTS—Retrospective analyses showed that adherence to OHA therapy ranged from 36 to 93% in patients remaining on treatment for 6–24 months. Prospective electronic monitoring studies documented that patients took 67–85% of OHA doses as prescribed. Electronic monitoring identified poor compliers for interventions that improved adherence (61–79%; P < 0.05). Young patients filled prescriptions for one-third of prescribed insulin doses. Insulin adherence among patients with type 2 diabetes was 62–64%.

CONCLUSIONS—This review confirms that many patients for whom diabetes medication was prescribed were poor compliers with treatment, including both OHAs and insulin. However, electronic monitoring systems were useful in improving adherence for individual patients. Similar electronic monitoring systems for insulin administration could help healthcare providers determine patients needing additional support.
Development of a Diabetes Diet-Related Quality-of-Life Scale
Authors: Sato Eiko , Suzukamo Yoshimi , Miyashita Mitsunori , Kazuma Keiko
Published: March 2007

OBJECTIVE—The purpose of this study was to assess the reliability and validity of the Diabetes Diet-Related Quality-of-Life (DDRQOL) scale, which is a measure of the influence of diet therapy on patients’ quality of life (QOL).

RESEARCH DESIGN AND METHODS—Patients with type 2 diabetes (n = 236) who were being treated on an outpatient basis were asked to complete the self-administered DDRQOL instrument. The factor validity, convergent and discriminant validity, internal consistency, and reproducibility of the DDRQOL scale were then assessed. Spearman’s rank correlation coefficients among the DDRQOL scale and each of the SF-36 subscale scores were calculated to evaluate its convergent and discriminant validity.

RESULTS—Based on the results of the factor analysis, the following seven subscales were adopted for the DDRQOL: “satisfaction with diet,” “burden of diet therapy,” “perceived merits of diet therapy,” “general perception of diet,” “restriction of social functions,” “vitality,” and “mental health.” As hypothesized, the DDRQOL scale was associated with each of the SF-36 subscales, with convergent and discriminant validity being generally exhibited. Cronbach’s α-coefficient was between 0.71 and 0.84, suggesting strong internal consistency. The intraclass correlation coefficient of the subscales, with the results of a test-retest conducted 2 weeks later, was between 0.46 and 0.75, suggesting some degree of reproducibility.

CONCLUSIONS—These findings indicate that the DDRQOL scale has a reasonable degree of reliability and validity, and its application for the assessment of the needs of a patient’s diet and the evaluation of diet education with regard to QOL is awaited.
The Coping Styles of Adolescents With Type 1 Diabetes Are Associated With Degree of Metabolic Control
Authors: Graue Marit , Wentzel-Larsen Tore , Bru Edvin , Hanestad Berit Rokne , Søvik Oddmund
Published: March 2007

OBJECTIVE—To systematically study the various coping styles in a population-based sample of adolescents with type 1 diabetes, exploring the association of different coping styles with metabolic control and adolescent self-reported diabetes-related quality of life.

RESEARCH DESIGN AND METHODS—Of a total population of 116 adolescents with type 1 diabetes (age 13–18 years), 103 (89%) participated in the study, completing a questionnaire to obtain information on coping styles and perception of diabetes-specific quality of life. The mean age (±SD) was 14.9 ± 1.6 years, diabetes duration 7.1 ± 3.8 years, HbA1c 9.4 ± 1.6%, and male-to-female ratio 52:51.

RESULTS—There was a significant correlation between higher HbA1c values and higher degree of mental (r = 0.25, P < 0.05) and behavioral (r = 0.33, P < 0.01) disengagement and aggressive coping (r = 0.33, P < 0.01). Stepwise multiple regression analyses indicated that greater use of aggressive coping (P < 0.05) and behavioral disengagement (P < 0.05) were significantly related to increase in HbA1c. Greater use of active coping (P < 0.05) was significantly related to a decrease in HbA1c. Partial correlation analysis showed that lower scores on diabetes-specific quality of life were significantly related to greater use of emotion-focused coping (r = −0.22 to −0.49). Stepwise multiple regression analyses showed that greater use of mental disengagement was significantly related to lower degree of perceived diabetes-related impact.

CONCLUSIONS—Poor metabolic control and lower degree of diabetes-related quality of life are associated with greater use of emotion-focused coping in adolescents with type 1 diabetes.
Adipocytokines Attenuate the Association Between Visceral Adiposity and Diabetes in Older Adults
Authors: Kanaya Alka M. , Harris Tamara , Goodpaster Bret H. , Tylavsky Fran , Cummings Steven R. ,   for the Health, Aging, and Body Composition (ABC) Study
Published: March 2007

OBJECTIVE—To examine whether adiponectin is independently associated with diabetes and whether adiponectin and other adipocytokines account for the relationship between fat and diabetes.

RESEARCH DESIGN AND METHODS—A nested case-control study from the Health, Aging, and Body Composition (Health ABC) study. We measured four adipocytokines: adiponectin, interleukin (IL)-6, tumor necrosis factor-α, and plasminogen activator inhibitor 1 (PAI-1). Regional fat area was determined by computed tomography scan. The 519 case subjects had diabetes defined by fasting plasma glucose level ≥126 mg/dl or by use of diabetes medications. The 519 control subjects had normal glucose tolerance and were matched by sex, race, and study site. Sex-specific logistic models were adjusted for age, race, site, total adiposity, smoking, and physical activity.

RESULTS—Higher adiponectin levels were associated with lower risk of diabetes (P < 0.001). Visceral fat was the only adiposity measure associated with diabetes after adjusting for BMI (odds ratio 3.0 [2.1–4.3] in women and 1.3 [1.0–1.6] in men, P < 0.001 between-sex comparison). Adipocytokines attenuated the association between visceral fat and diabetes for both sexes but more strongly in men (women 2.3 [1.5–3.3], men 1.1 [0.9–1.4]). In men, adiponectin, IL-6, and PAI-1 remained independently associated with diabetes after adjusting for fat depots; in women, adiponectin was the only independently associated adipocytokine. Controlling for insulin, HDL, triglycerides, and blood pressure did not change these results.

CONCLUSIONS—Adiponectin is associated with lower odds of diabetes in older men and women. Whereas several adipocytokines explained the relationship between visceral adiposity and diabetes in men, only adiponectin partially mediated this association among women.
Improved Glycemic Control Without Weight Gain Using Triple Therapy in Type 2 Diabetes
Authors: Strowig Suzanne M. , Avilés-Santa M. Larissa , Raskin Philip
Published: March 2007

OBJECTIVE—To evaluate the safety and effectiveness of triple therapy using insulin, metformin, and a thiazolidinedione following a course of dual therapy using insulin and metformin or insulin and a thiazolidinedione in type 2 diabetes.

RESEARCH DESIGN AND METHODS—Twenty-eight type 2 diabetic subjects using insulin monotherapy (baseline HbAlc level 8.5%) who had been randomly assigned to insulin (INS) and metformin (MET) (INS + MET, n = 14) or INS and the thiazolidinedione troglitazone (TGZ) (INS + TGZ, n = 14) (dual therapy) for 4 months were given INS, MET, and TGZ (triple therapy: INS + MET, add TGZ; or INS + TGZ, add MET) for another 4 months. The INS dose was not increased.

RESULTS—HbA1c levels decreased in both groups during dual therapy and improved further during triple therapy (INS + MET 7.0 ± 0.8, INS + TGZ 6.2 ± 0.8, P < 0.0001; INS + MET, add TGZ 6.1 ± 0.4%, P < 0.001; INS + TGZ, add MET 5.8 ± 0.6%, P < 0.05; and INS + TGZ vs. INS + MET, P = 0.02). Significant reductions in total daily insulin dose occurred in the INS + TGZ (−14.1 units, P < 0.0001), INS + TGZ add MET (−13.7 units, P < 0.01), and the INS + MET add TGZ groups (−17.3 units, P < 0.003), but not in the INS + MET group (−3.2 units) (INS + TGZ vs. INS + MET P < 0.05). Subjects in the INS + TGZ group experienced significant weight gain (4.4 ± 2.7 kg, P < 0.0005). No weight gain occurred in the INS + MET, INS + MET add TGZ, and INS + TGZ add MET groups.

CONCLUSIONS—Triple therapy using INS, MET, and TGZ resulted in lower HbAlc levels and total daily insulin dose than during dual therapy. The use of triple therapy resulted in 100% of subjects achieving an HbAlc <7.0%, while decreasing the dose of INS. Weight gain was avoided when MET therapy preceded the addition of TGZ therapy. The addition of TGZ resulted in the greatest reductions in HbAlc levels and insulin dose. Triple therapy using INS, MET, and a thiazolidinedione (such as TGZ) can be a safe and effective treatment in type 2 diabetes.
Elevated Plasma Glucose-Dependent Insulinotropic Polypeptide Associates With Hyperinsulinemia in Impaired Glucose Tolerance
Authors: Theodorakis Michael J. , Carlson Olga , Muller Denis C. , Egan Josephine M.
Published: March 2007

OBJECTIVE—The role of gut-derived incretin, glucose-dependent insulinotropic polypeptide (also known as gastric inhibitory peptide [GIP]), in compensatory β-cell hypersecretion during insulin-resistant states and in transition to β-cell failure in type 2 diabetes is unknown.

RESEARCH DESIGN AND METHODS—We carried out oral glucose tolerance testing followed by blood sampling 10 times for 2 h on 68 age- and BMI-matched participants of the Baltimore Longitudinal Study on Aging (BLSA) with normal glucose tolerance (34 subjects), impaired glucose tolerance (IGT) (18 subjects with both impaired fasting and 2-h plasma glucose levels), and type 2 diabetes (16 subjects with both diabetic fasting and 2-h plasma glucose levels). We assayed plasma glucose, insulin, C-peptide, glucagon, and intact and total GIP levels and quantitated glucose and hormone responses to the oral glucose tolerance test. We also compared GIP and insulin release and sensitivity indexes between groups.

RESULTS—After glucose ingestion, subjects with IGT had both hyperinsulinemia and hyperemia, while subjects with type 2 diabetes had both β- and GIP-cell deficiency. In the former group, there was also a significant positive correlation between the augmented plasma intact and total GIP levels and both fasting and post-oral glucose load plasma insulin levels.

CONCLUSIONS— Elevated plasma GIP levels are correlated with hyperinsulinemia in the impaired glucose-tolerant state, whereas type 2 diabetes is associated with a failure to secrete adequate amounts of both GIP and insulin, indicating a common pathway of resistance to and eventually failure of glucose responsiveness in β- and GIP-cells.
Treatment of Diabetic Ketoacidosis With Subcutaneous Insulin Aspart
Authors: Umpierrez Guillermo E. , Cuervo Ruben , Karabell Ana , Latif Kashif , Freire Amado X. , Kitabchi Abbas E.
Published: March 2007

OBJECTIVE—In this prospective, randomized, open trial, we compared the efficacy and safety of aspart insulin given subcutaneously at different time intervals to a standard low-dose intravenous (IV) infusion protocol of regular insulin in patients with uncomplicated diabetic ketoacidosis (DKA).

RESEARCH DESIGN AND METHODS—A total of 45 consecutive patients admitted with DKA were randomly assigned to receive subcutaneous (SC) aspart insulin every hour (SC-1h, n = 15) or every 2 h (SC-2h, n = 15) or to receive IV infusion of regular insulin (n = 15). Response to medical therapy was evaluated by assessing the duration of treatment until resolution of hyperglycemia and ketoacidosis. Additional end points included total length of hospitalization, amount of insulin administration until resolution of hyperglycemia and ketoacidosis, and number of hypoglycemic events.

RESULTS—Admission biochemical parameters in patients treated with SC-1h (glucose: 44 ± 21 mmol/l [means ± SD], bicarbonate: 7.1 ± 3 mmol/l, pH: 7.14 ± 0.09) were similar to those treated with SC-2h (glucose: 42 ± 21 mmol/l, bicarbonate: 7.6 ± 4 mmol/l, pH: 7.15 ± 0.12) and IV regular insulin (glucose: 40 ± 13 mmol/l, bicarbonate 7.1 ± 4 mmol/l, pH: 7.11 ± 0.17). There were no statistical differences in the mean duration of treatment until correction of hyperglycemia (6.9 ± 4, 6.1 ± 4, and 7.1 ± 5 h) or until resolution of ketoacidosis (10 ± 3, 10.7 ± 3, and 11 ± 3 h) among patients treated with SC-1h and SC-2h or with IV insulin, respectively (NS). There was no mortality and no differences in the length of hospital stay, total amount of insulin administration until resolution of hyperglycemia or ketoacidosis, or the number of hypoglycemic events among treatment groups.

CONCLUSIONS—Our results indicate that the use of subcutaneous insulin aspart every 1 or 2 h represents a safe and effective alternative to the use of intravenous regular insulin in the management of patients with uncomplicated DKA.
Sagittal Abdominal Diameter Is a Strong Anthropometric Marker of Insulin Resistance and Hyperproinsulinemia in Obese Men
Authors: Risérus Ulf , Ärnlöv Johan , Brismar Kerstin , Zethelius Björn , Berglund Lars , Vessby Bengt
Published: March 2007

OBJECTIVE—It is clinically important to find noninvasive markers of insulin resistance and hyperproinsulinemia because they both predict cardiovascular and diabetes risk. Sagittal abdominal diameter (SAD) or “supine abdominal height” is a simple anthropometric measure previously shown to predict mortality in men, but its association with insulin resistance and hyperproinsulinemia is unknown.

RESEARCH DESIGN AND METHODS—In a common high-risk group of 59 moderately obese men (aged 35–65 years, BMI 32.6 ± 2.3 kg/m2), we determined anthropometry (SAD, BMI, waist girth, and waist-to-hip ratio [WHR]); insulin sensitivity (euglycemic-hyperinsulinemic clamp); and plasma concentrations of intact proinsulin, specific insulin, C-peptide, glucose, and serum IGF binding protein-1 (IGFBP-1). To compare SAD with other anthropometric measures, univariate and multiple regression analyses were used to determine correlations between anthropometric and metabolic variables.

RESULTS—SAD showed stronger correlations to all measured metabolic variables, including insulin sensitivity, than BMI, waist girth, and WHR. SAD explained the largest degree of variation in insulin sensitivity (R2 = 0.38, P < 0.0001) compared with other anthropometric measures. In multiple regression analyses, including all anthropometric measures, SAD was the only independent anthropometric predictor of insulin resistance (P < 0.001) and hyperproinsulinemia (P < 0.001).

CONCLUSIONS—In obese men, SAD seems to be a better correlate of insulin resistance and hyperproinsulinemia (i.e., cardiovascular risk) than other anthropometric measures. In overweight and obese individuals, SAD could represent a simple, cheap, and noninvasive tool that could identify the most insulin resistant in both the clinic and clinical trials evaluating insulin sensitizers. These results need confirmation in larger studies that also include women and lean subjects.
Cost-Effectiveness Analysis of Different Screening Procedures for Type 2 Diabetes
Authors: Icks Andrea , Haastert Burkhard , Gandjour Afschin , John Jürgen , Löwel Hannelore , Holle Rolf , Giani Guido , Rathmann Wolfgang ,   on behalf of the KORA Study Group
Published: March 2007

OBJECTIVE—To compare the cost-effectiveness of different type 2 diabetes screening strategies using population-based data (KORA Survey; Augsburg, Germany; subjects aged 55–74 years), including participation data.

RESEARCH DESIGN AND METHODS—The decision analytic model, which had a time horizon of 1 year, used the following screening strategies: fasting glucose testing, the oral glucose tolerance test (OGTT) following fasting glucose testing in impaired fasting glucose (IFG) (fasting glucose + OGTT), OGTT only, and OGTT if HbA1c was >5.6% (HbA1c + OGTT), all with or without first-step preselection (p). The main outcome measures were costs (in Euros), true-positive type 2 diabetic cases, incremental cost-effectiveness ratios (ICERs), third-party payers, and societal perspectives.

RESULTS—After dominated strategies were excluded, the OGTT and HbA1c + OGTT from the perspective of the statutory health insurance remained, as did fasting glucose + OGTT and HbA1c + OGTT from the societal perspective. OGTTs (€4.90 per patient) yielded the lowest costs from the perspective of the statutory health insurance and fasting glucose + OGTT (€10.85) from the societal perspective. HbA1c + OGTT was the most expensive (€21.44 and €31.77) but also the most effective (54% detected cases). ICERs, compared with the next less effective strategies, were €771 from the statutory health insurance and €831 from the societal perspective. In the Monte Carlo analysis, dominance relations remained unchanged in 100 and 68% (statutory health insurance and societal perspective, respectively) of simulated populations.

CONCLUSIONS—The most effective screening strategy was HbA1c combined with OGTT because of high participation. However, costs were lower when screening with fasting glucose tests combined with OGTT or OGTT alone. The decision regarding which is the most favorable strategy depends on whether the goal is to identify a high number of cases or to incur lower costs at reasonable effectiveness.
Lack of Agreement Between the Revised Criteria of Impaired Fasting Glucose and Impaired Glucose Tolerance in Children With Excess Body Weight
Authors: Gómez-Díaz Rita , Aguilar-Salinas Carlos A. , Morán-Villota Segundo , Barradas-González Rosalinda , Herrera-Márquez Rocio , Cruz López Miguel , Kumate Jesus , Wacher Niels H.
Published: March 2007

OBJECTIVE—The aim of this study was to describe the agreement between impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) in children with excess body weight using the original and the revised definitions of IFG.

RESEARCH DESIGN AND METHODS—Obese and overweight children aged 4–17 years were included (n = 533). Anthropometric parameters and biochemical tests (fasting and 2-h glucose tests after an oral glucose load [1.75 g/kg]) were performed. Case subjects with a fasting plasma glucose ≥126 mg/dl were excluded. The diagnostic parameters of the original and the revised definitions of IFG for detecting IGT were estimated. The analysis of agreement between these categories was made using the κ test.

RESULTS—The prevalence of IFG increased from 6.2 to 13.3% using the new criteria. The prevalence of IFG became closer to the prevalence of IGT (14.8%). The revised criteria increased the sensitivity from 26.6 to 36.7%. However, the new IFG definition was not useful for identifying IGT cases. Of the 71 case subjects with IFG, only 29 (40.8%) had IGT. In addition, 50 case subjects with IGT (9.4%) and 13 with diabetes (2.4%) had a fasting glycemia <100 mg/dl. A poor agreement was found between the 2003 IFG definition and abnormal 2-h postchallenge plasma glucose (κ = 0.359). The proportion of false-positive cases increased (36.3–59.1%) under the new definition.

CONCLUSIONS—The new definition modestly increases the sensitivity of IFG for detecting IGT in children with excess body weight. Despite this, more than one-half of these cases are not detected. In addition, the false-positive rate was increased by 61%.
Cardiovascular Disease Risk Factors Predict the Development of Type 2 Diabetes
Authors: D’Agostino Ralph B. , Hamman Richard F. , Karter Andrew J. , Mykkanen Leena , Wagenknecht Lynne E. , Haffner Steven M. ,   for the Insulin Resistance Atherosclerosis Study Investigators
Published: March 2007

OBJECTIVE—In a few previous studies, cardiovascular disease (CVD) risk factors (RFs) have been shown to predict diabetes. Our objective was to determine whether the presence of CVD RFs predict the eventual development of diabetes after controlling for known RFs, such as directly measured insulin resistance and obesity.

RESEARCH DESIGN AND METHODS—We studied 872 participants with normal or impaired glucose tolerance (IGT) who were enrolled at baseline in the Insulin Resistance Atherosclerosis Study (IRAS). Of these, 143 (16%) developed type 2 diabetes in 5 years. Using these participants, a series of logistic regression models were fit to address the question.

RESULTS—Significant RFs for developing type 2 diabetes included high plasminogen activator inhibitor-1, hypertension, high triglycerides, low levels of HDL cholesterol, and IGT. The 5-year cumulative incidence of type 2 diabetes by the number of RFs (0–5) was as follows: no RFs, 11 of 230 = 5%; one RF, 31 of 278 = 11%; two RFs, 36 of 202 = 18%; three RFs, 41 of 110 = 37%; four RFs, 19 of 42 = 45%; and five RFs, 5 of 10 = 50% (P < 0.001). The odds ratio (OR) for conversion to type 2 diabetes for each additional RF was 2.1 (95% CI 1.78–2.46) after adjusting for age, sex, ethnicity, and center. After further adjustment for insulin resistance, determined by the frequently sampled intravenous glucose tolerance test and waist circumference, each additional CVD RF increased the risk of type 2 diabetes significantly (OR 1.81, 95% CI 1.49–2.20).

CONCLUSIONS—Individuals with multiple CVD RFs are at increased risk of type 2 diabetes, which is only partially mediated by insulin resistance or central adiposity. This information should be useful for identifying high-risk patients for developing diabetes through RF assessments.
Specific Effects of Biliopancreatic Diversion on the Major Components of Metabolic Syndrome
Authors: Scopinaro Nicola , Marinari Giuseppe Maria , Camerini Giovanni Bruno , Papadia Francesco Saverio , Adami Gian Franco
Published: March 2007

OBJECTIVE—Gastric bypass and biliopancreatic diversion (BPD) are known to have a beneficial effect on glucose metabolism superior to that of the other bariatric operations. Thanks to its excellent weight loss results and to its specific actions, BPD has proven able to guarantee permanent normalization of serum glucose, triglygeride, and cholesterol levels in the vast majority, if not the totality, of operated patients. However, clinical studies on the duration of these effects in large patient populations are still lacking.

RESEARCH DESIGN AND METHODS—The files of 312 BPD obese patients with type 2 diabetes operated on from June 1984 to January 1993 were examined. Pre- and postoperative serum glucose, triglyceride, and cholesterol levels, along with arterial pressure measurements, were considered.

RESULTS—After BPD, fasting serum glucose concentration fell within normal values in all but two of the operated subjects and remained in the physiological range in all but six up until 10 years. Serum triglyceride and total cholesterol steadily normalized in all subjects with abnormally high preoperative values, and arterial hypertension disappeared in the vast majority of the preoperatively hypertensive patients.

CONCLUSIONS—BPD proved able to reverse all the major components of the metabolic syndrome in nearly all the operated subjects, with results being strictly maintained over a 10-year follow-up period. This outcome, which far exceeds those following similar weight loss at short or long term obtained by any other means, confirms the existence of specific actions of BPD on the major components of metabolic syndrome.
Glycated and Oxidized Protein Degradation Products Are Indicators of Fasting and Postprandial Hyperglycemia in Diabetes
Authors: Ahmed Naila , Babaei-Jadidi Roya , Howell Scott K. , Thornalley Paul J. , Beisswenger Paul J.
Published: March 2007

OBJECTIVE—To assess the relative importance of fasting and postprandial hyperglycemia to vascular dysfunction in diabetes, we have measured indicators of glycation, oxidative and nitrosative stress in subjects with type 1 diabetes, and different postprandial glucose patterns.

RESEARCH DESIGN AND METHODS—Plasma and urinary levels of specific arginine- and lysine-derived advanced glycation end products, as well as oxidative and nitrosative products, were measured by liquid chromatography with triple quadrupole mass spectrometric detection (LC-MS/MS) after 2 months of treatment with insulin lispro or human regular insulin in 21 subjects participating in a cross-over study. Hb-bound early glycation (Amadori) products were also measured after each treatment period by high-performance liquid chromatography (fructosyl-valine Hb or HbA1c [A1C]:Diamat) and fructosyl-lysine Hb by LC-MS/MS (A1C:fructosyl-lysine).

RESULTS—In diabetic patients, the concentrations of protein glycation and oxidation-free adducts increased up to 10-fold, while urinary excretion increased up to 15-fold. Decreasing postprandial hyperglycemia with lispro gave 10–20% decreases of the major free glycation adducts, hydroimidazolones derived from methylglyoxal and 3-deoxyglucosone, and glyoxal-derived Nε-carboxymethyl-lysine. No differences were observed in A1C:Diamat or A1C:fructosyl-lysine with lispro or regular insulin therapy in spite of significant decreases in postprandial glycemia with lispro.

CONCLUSIONS—We conclude that the profound increases in proteolytic products of proteins modified by advanced glycation endproducts in diabetic patients are responsive to changes in mean hyperglycemia and also show responses to changes in postprandial hyperglycemia.
Dietary Glycemic Index and Glycemic Load, Carbohydrate and Fiber Intake, and Measures of Insulin Sensitivity, Secretion, and Adiposity in the Insulin Resistance Atherosclerosis Study
Authors: Liese Angela D. , Schulz Mandy , Fang Fang , Wolever Thomas M.S. , D’Agostino Ralph B. , Sparks Karen C. , Mayer-Davis Elizabeth J.
Published: March 2007

OBJECTIVE—We studied the association of digestible carbohydrates, fiber intake, glycemic index, and glycemic load with insulin sensitivity (SI), fasting insulin, acute insulin response (AIR), disposition index, BMI, and waist circumference.

RESEARCH DESIGN AND METHODS—Data on 979 adults with normal (67%) and impaired (33%) glucose tolerance from the Insulin Resistance Atherosclerosis Study (1992–1994) were analyzed. Usual dietary intake was assessed via a 114-item interviewer-administered food frequency questionnaire from which nutrient intakes were estimated. Published glycemic index values were assigned to food items and average dietary glycemic index and glycemic load calculated per subject. SI and AIR were determined by frequently sampled intravenous glucose tolerance test. Disposition index was calculated by multiplying SI with AIR. Multiple linear regression modeling was employed.

RESULTS—No association was observed between glycemic index and SI, fasting insulin, AIR, disposition index, BMI, or waist circumference after adjustment for demographic characteristics or family history of diabetes, energy expenditure, and smoking. Associations observed for digestible carbohydrates and glycemic load, respectively, with SI, insulin secretion, and adiposity (adjusted for demographics and main confounders) were entirely explained by energy intake. In contrast, fiber was associated positively with SI and disposition index and inversely with fasting insulin, BMI, and waist circumference but not with AIR.

CONCLUSION—Carbohydrates as reflected in glycemic index and glycemic load may not be related to measures of insulin sensitivity, insulin secretion, and adiposity. Fiber intake may not only have beneficial effects on insulin sensitivity and adiposity, but also on pancreatic functionality.
Anthropometry, Glucose Tolerance, and Insulin Concentrations in Indian Children
Authors: Krishnaveni Ghattu V. , Hill Jacqueline C. , Leary Samantha D. , Veena Sargoor R. , Saperia Julia , Saroja Anandathirtha , Karat Samuel C. , Fall Caroline H.D.
Published: March 2007

OBJECTIVE—The purpose of this study was to test the hypothesis that the environment experienced by fetuses of mothers with gestational diabetes mellitus (GDM) and mothers with higher glucose concentrations that are in the normal range causes increased adiposity and altered glucose/insulin metabolism in childhood.

RESEARCH DESIGN AND METHODS—Children (n = 630) whose mothers were tested for glucose tolerance during pregnancy had detailed anthropometry performed at birth and annually thereafter. At 5 years, plasma glucose and insulin concentrations were measured in the children (2-h oral glucose tolerance test) and their fathers (fasting samples only).

RESULTS—Newborns of diabetic mothers (n = 41) were larger in all body measurements than control newborns (babies with nondiabetic parents). At 1 year, these differences had diminished and were not statistically significant. At 5 years, female offspring of diabetic mothers had larger subscapular and triceps skinfold thicknesses (P = 0.01) and higher 30- and 120-min insulin concentrations (P < 0.05) than control children. Offspring of diabetic fathers (n = 41) were lighter at birth than control children (P < 0.001); they showed no differences in anthropometry at 5 years. In control children, skinfold thickness and 30-min insulin concentrations were positively related to maternal insulin area under the curve, and skinfold thicknesses were related to paternal fasting insulin concentrations independently of the parents’ skinfold thickness and socioeconomic status.

CONCLUSIONS—Maternal GDM is associated with adiposity and higher glucose and insulin concentrations in female offspring at 5 years. The absence of similar associations in offspring of diabetic fathers suggests a programming effect in the diabetic intrauterine environment. More research is needed to determine whether higher maternal glucose concentrations in the nondiabetic range have similar effects.