bluuebunny/crossref_metadata_2025 huggingface dataset:
Applying Diabetes-Related Prevention Quality Indicators to a National Cohort of Veterans With Diabetes
Authors: Helmer Drew A. , Tseng Chin-Lin , Brimacombe Michael , Rajan Mangala , Stiptzarov Nikolay , Pogach Leonard
Published: March 2007

OBJECTIVE—The Prevention Quality Indicators (PQIs) are measures of hospitalizations that reflect quality of ambulatory care. We applied the PQIs of metabolic decompensation to Veterans Health Administration (VHA) utilizers with diabetes. We identified patient-level characteristics associated with hospitalization for metabolic decompensation, developed a risk-adjustment model for the measures, and compared regional network performance using these PQIs.

RESEARCH DESIGN AND METHODS—This was a retrospective cohort study of 406,575 veterans with diabetes who used the VHA between 1997 and 1999. The outcomes were the PQIs of uncontrolled diabetes, short-term complications, or a combined measure. Patient-level variables were identified from administrative databases. Variation in performance of the networks was compared between full risk adjustment and age and sex adjustment only.

RESULTS—In fiscal year 1999, there were 1,719 VHA discharges (4.2 per 1,000 cohort members) for uncontrolled and short-term complications of diabetes. A logistic regression model including age, sex, marital status, Charlson Comorbidity Index, mental health condition, insulin use, and oral antiglycemic medication use was developed for risk adjustment of the combined PQI. Full risk adjustment changed performance ranks of the networks using the combined PQI outcome relative to age and sex adjustment only. Ten networks remained in the same quartile of performance, five moved one quartile, and seven moved two or more quartiles.

CONCLUSIONS—The PQIs of uncontrolled and short-term complications of diabetes are uncommon outcomes among veterans with diabetes and should be used only as a combined outcome. More complete risk adjustment should be used when comparing systems of care using the combined measure.
The Singapore Impaired Glucose Tolerance Follow-Up Study
Authors: Wong Moh-Sim , Gu Ken , Heng Derrick , Chew Suok-Kai , Chew Loy-Soong , Tai E. Shyong
Published: March 2007

OBJECTIVE—To 1) document the change in glucose tolerance for subjects with normal glucose tolerance (NGT) and impaired glucose tolerance (IGT) over time, 2) identify baseline factors associated with worsening of glucose tolerance, and 3) determine whether cardiovascular disease (CVD) risk factors associated with IGT improved in tandem with glucose tolerance.

RESEARCH DESIGN—Subjects with IGT and NGT (matched for age, sex, and ethnic group) were identified from a cross-sectional survey conducted in 1992. Subjects with IGT (297) and NGT (298) (65.0%) were reexamined in 2000. Glucose tolerance (assessed by 75-g oral glucose tolerance test), anthropometric data, serum lipids, blood pressure, and insulin resistance were determined at baseline and at the follow-up examination.

RESULTS—For NGT subjects, 14.0% progressed to IGT and 4.3% to diabetes over 8 years. For IGT subjects, 41.4% reverted to NGT, 23.0% remained impaired glucose tolerant, and 35.1% developed diabetes. Obesity, hypertriglyceridemia, higher blood pressure, increased insulin resistance, and lower HDL cholesterol at baseline were associated with worsening of glucose tolerance in both IGT and NGT subjects. Those with IGT who reverted to NGT remained more obese and had higher blood pressure than those with NGT in both 1992 and 2000. However, serum triglyceride, HDL cholesterol, and insulin resistance values in 2000 became indistinguishable from those of subjects who maintained NGT throughout the study period.

CONCLUSIONS—Some, but not all, CVD risk factors associated with IGT and with the risk of future diabetes normalize when glucose tolerance normalizes. Continued surveillance and treatment in subjects with IGT, even after they revert to NGT, may be important in the prevention of CVD.
Integrating Medical Management With Diabetes Self-Management Training
Authors: Polonsky William H. , Earles Jay , Smith Susan , Pease Donna J. , Macmillan Mary , Christensen Reed , Taylor Thomas , Dickert Judy , Jackson Richard A.
Published: March 2007

OBJECTIVE—This study evaluated the Diabetes Outpatient Intensive Treatment (DOIT) program, a multiday group education and skills training experience combined with daily medical management, followed by case management over 6 months. Using a randomized control design, the study explored how DOIT affected glycemic control and self-care behaviors over a short term. The impact of two additional factors on clinical outcomes were also examined (frequency of case management contacts and whether or not insulin was started during the program).

RESEARCH DESIGN AND METHODS—Patients with type 1 and type 2 diabetes in poor glycemic control (A1c >8.5%) were randomly assigned to DOIT or a second condition, entitled EDUPOST, which was standard diabetes care with the addition of quarterly educational mailings. A total of 167 patients (78 EDUPOST, 89 DOIT) completed all baseline measures, including A1c and a questionnaire assessing diabetes-related self-care behaviors. At 6 months, 117 patients (52 EDUPOST, 65 DOIT) returned to complete a follow-up A1c and the identical self-care questionnaire.

RESULTS—At follow-up, DOIT evidenced a significantly greater drop in A1c than EDUPOST. DOIT patients also reported significantly more frequent blood glucose monitoring and greater attention to carbohydrate and fat contents (ACFC) of food compared with EDUPOST patients. An increase in ACFC over the 6-month period was associated with improved glycemic control among DOIT patients. Also, the frequency of nurse case manager follow-up contacts was positively linked to better A1c outcomes. The addition of insulin did not appear to be a significant contributor to glycemic change.

CONCLUSIONS—DOIT appears to be effective in promoting better diabetes care and positively influencing glycemia and diabetes-related self-care behaviors. However, it demands significant time, commitment, and careful coordination with many health care professionals. The role of the nurse case manager in providing ongoing follow-up contact seems important.
Cinnamon Improves Glucose and Lipids of People With Type 2 Diabetes
Authors: Khan Alam , Safdar Mahpara , Ali Khan Mohammad Muzaffar , Khattak Khan Nawaz , Anderson Richard A.
Published: March 2007

OBJECTIVE—The objective of this study was to determine whether cinnamon improves blood glucose, triglyceride, total cholesterol, HDL cholesterol, and LDL cholesterol levels in people with type 2 diabetes.

RESEARCH DESIGN AND METHODS—A total of 60 people with type 2 diabetes, 30 men and 30 women aged 52.2 ± 6.32 years, were divided randomly into six groups. Groups 1, 2, and 3 consumed 1, 3, or 6 g of cinnamon daily, respectively, and groups 4, 5, and 6 were given placebo capsules corresponding to the number of capsules consumed for the three levels of cinnamon. The cinnamon was consumed for 40 days followed by a 20-day washout period.

RESULTS—After 40 days, all three levels of cinnamon reduced the mean fasting serum glucose (18–29%), triglyceride (23–30%), LDL cholesterol (7–27%), and total cholesterol (12–26%) levels; no significant changes were noted in the placebo groups. Changes in HDL cholesterol were not significant.

CONCLUSIONS—The results of this study demonstrate that intake of 1, 3, or 6 g of cinnamon per day reduces serum glucose, triglyceride, LDL cholesterol, and total cholesterol in people with type 2 diabetes and suggest that the inclusion of cinnamon in the diet of people with type 2 diabetes will reduce risk factors associated with diabetes and cardiovascular diseases.
Plasma Adiponectin Is an Independent Predictor of Type 2 Diabetes in Asian Indians
Authors: Snehalatha Chamukuttan , Mukesh Bheekamchand , Simon Mary , Viswanathan Vijay , Haffner Steven M. , Ramachandran Ambady
Published: March 2007

OBJECTIVE—Adiponectin, secreted by fat cells, has regulatory functions on energy metabolism. Its low levels are predictive of future development of diabetes. Because no studies on the regulatory role of adiponectin in glucose homeostasis in Asian Indians exist, this analysis was performed to determine the prospective association of adiponectin and diabetes in subjects with impaired glucose tolerance (IGT).

RESEARCH DESIGN AND METHODS—Baseline values of plasma adiponectin, results of anthropometry, fasting and 2-h plasma glucose levels, HbA1c, results of lipid profile, and insulin resistance were analyzed in 91 subjects with IGT (53 men and 38 women) in a primary prevention study. Reassessment of glucose tolerance was performed during 1-year review. The predictive nature of adiponectin for development of diabetes was assessed using univariate and multiple logistic regression analyses. A control group comprising healthy, normoglycemic individuals was used for comparison.

RESULTS—At follow-up, diabetes had developed in 25 of the 91 study subjects. The mean baseline adiponectin level was lower in the diabetic subjects than in the nondiabetic subjects (11.3 ± 5.5 vs. 16.7 ± 7.6 μg/ml, P = 0.0017). Low adiponectin level was a strong predictor of future development of diabetes, and HbA1c also showed a positive predictive association. Women had higher adiponectin levels (16.4 ± 6.1 μg/ml) than men (13.9 ± 7.6 μg/ml) (P = 0.035).

CONCLUSIONS—In Asian Indians, low plasma adiponectin level was predictive of future development of diabetes.
Racial Variation in the Control of Diabetes Among Elderly Medicare Managed Care Beneficiaries
Authors: McBean A. Marshall , Huang Zhen , Virnig Beth A. , Lurie Nicole , Musgrave Dorothea
Published: March 2007

OBJECTIVE—To examine racial variation in the poor control of GHb, a GHb value >9.5%, or GHb not tested in 1999 among Medicare beneficiaries aged 65–75 years enrolled in managed care plans.

RESEARCH DESIGN AND METHODS—The National Committee on Quality Assurance provides person-level data regarding diabetes care services and control for Medicare beneficiaries enrolled in managed care to the Centers for Medicare and Medicaid Services (CMS). We merged this information with information on each individual’s race, as well as other person-level and plan-level characteristics obtained from CMS. Bivarate and multivariate analyses were performed.

RESULTS—The overall rate of poor GHb control was 32.7%. The age- and sex-adjusted rate of poor control among whites was 32.0%. This rate was significantly higher than the rate among Asians (24.7%) but significantly lower than the rate among blacks (40.6%) and Hispanics (36.5%) (P < 0.001). An increase in the number of comprehensive diabetes care measures received by an individual was associated with a significantly lower percentage of individuals with poor GHb control in all race groups. After controlling for the individual-level, plan-level, and diabetes care measure variables, the difference in GHb control between Asians and whites disappeared. However, blacks and Hispanics continued to have significantly higher rates of poor control than whites.

CONCLUSIONS—There is room for significant reduction in the number of patients with poor control of GHb among all races, particularly among blacks and Hispanics.
The Combined Effect of Triple Therapy With Rosiglitazone, Metformin, and Insulin Aspart in Type 2 Diabetic Patients
Authors: Poulsen Mikael Kjær , Henriksen Jan Erik , Hother-Nielsen Ole , Beck-Nielsen Henning
Published: March 2007

OBJECTIVE—Type 2 diabetes is caused by reduced insulin secretion and insulin resistance in skeletal muscle and liver. We tested the combination therapy with insulin aspart, rosiglitazone, and metformin with the purpose of treating all three defects in order to test the hypothesis that this “triple therapy” will normalize glucose metabolism.

RESEARCH DESIGN AND METHODS—Sixteen obese type 2 diabetic outpatients on human NPH or MIX (regular + NPH insulin) insulin twice daily were randomized to either triple therapy, i.e., insulin aspart (a rapid-acting insulin analog) at meals, metformin (which improves hepatic insulin sensitivity), and rosiglitazone (which improves peripheral insulin sensitivity), or to continue their NPH or MIX insulin twice daily for 6 months. Insulin doses were adjusted in both groups based on algorithms. HbA1c, insulin dose, hypoglycemic episodes, insulin sensitivity (clamp), hepatic glucose production (tracer), and diurnal profiles of plasma glucose and insulin were used in evaluating treatment.

RESULTS—In the triple therapy group, HbA1c declined from 8.8 to 6.8% (P < 0.01) without inducing severe hypoglycemic events. Postprandial hyperglycemia was generally avoided, and the diurnal profile of serum insulin showed fast and high peaks without any need to increase insulin dose. In the control group, the insulin dose was increased by 50%, but nevertheless both HbA1c and 24-h blood glucose profiles remained unchanged. Insulin sensitivity improved in both skeletal muscle and the liver in the triple therapy group, whereas no change was observed in the control group.

CONCLUSIONS—We conclude that treatment of the three major pathophysiological defects in type 2 diabetic subjects by triple therapy significantly improved glucose metabolism in obese type 2 diabetic subjects.
Plasma Adiponectin and Endogenous Glucose Production in Humans
Authors: Stefan Norbert , Stumvoll Michael , Vozarova Barbora , Weyer Christian , Funahashi Tohru , Matsuzawa Yuji , Bogardus Clifton , Tataranni P. Antonio
Published: March 2007

OBJECTIVE—High plasma adiponectin is associated with reduced risk of type 2 diabetes, probably a consequence of its insulin-sensitizing properties. In vivo data in rodents suggest that the insulin-sensitization responsible for improvement of glycemia occurs in muscle and liver. Whereas associations of plasma adiponectin with muscle insulin sensitivity in humans have been examined, this has not been done for the liver.

RESEARCH DESIGN AND METHODS—We therefore analyzed the relationship between fasting plasma adiponectin and basal endogenous glucose production [EGP]-basal) and insulin-suppressed EGP (EGP-insulin, isotope dilution technique) in 143 Pima Indians (94 with normal glucose tolerance, 36 with impaired glucose tolerance, and 16 with type 2 diabetes).

RESULTS—Fasting plasma adiponectin concentrations were negatively correlated with EGP-basal and EGP-insulin before (P = 0.006 and P < 0.0001, respectively) as well as after adjustment for age, sex, percent body fat, and insulin-stimulated whole-body glucose uptake (P = 0.007 and P = 0.0005, respectively).

CONCLUSIONS—These findings are compatible with the hypothesis that adiponectin increases hepatic insulin sensitivity. Consistent with data in animals, adiponectin may have generalized insulin-sensitizing effects in humans.
Did Publication of a Clinical Practice Guideline Recommendation to Screen for Type 2 Diabetes in Women With Gestational Diabetes Change Practice?
Authors: Clark Heather D. , Walraven Carl van , Code Cathy , Karovitch Alan , Keely Erin
Published: March 2007

OBJECTIVE—To determine whether women with previous gestational diabetes mellitus (GDM) were screened postpartum for type 2 diabetes according to the Canadian Diabetes Association (CDA) guidelines.

RESEARCH DESIGN AND METHODS—The 1998 CDA guidelines recommend that all women diagnosed with GDM be screened postpartum for type 2 diabetes using a 2-h 75-g oral glucose tolerance test (OGTT). The impact of and compliance with this expert opinion-based recommendation is unknown. All women who delivered at the Ottawa Hospital in 1997 (pre-guideline) and 2000 (post-guideline) with confirmed GDM were identified. Using population-based administrative databases, we determined the proportion of these women who had an OGTT, serum glucose test, or glycated hemoglobin (GHb) test in the first postpartum year. Women who had not undergone any blood work were excluded.

RESULTS—There were 131 women in 1997 and 123 women in 2000 with confirmed GDM. Of these, only 69 women in 1997 and 52 women in 2000 had blood work recorded in the database. None of these women had an OGTT performed in either period. We found a significant increase in the measurement of serum glucose (50 women pre-guideline [72.1%], 48 women post-guideline [92.3%], P < 0.05) and GHb (8 women pre-guideline [11.6%], 20 women post-guideline [38.5%], P < 0.01).

CONCLUSIONS—In our region, physicians are not following the CDA recommendations to screen women with GDM postpartum with an OGTT. However, we did find a significant increase in the measurement of serum glucose and GHb. Publication of expert opinion-based guidelines did not change the postpartum use of an OGTT in these women but may have increased the use of less reliable screening tests for type 2 diabetes.
Acarbose Improves Glycemic Control in Overweight Type 2 Diabetic Patients Insufficiently Treated With Metformin
Authors: Phillips Patrick , Karrasch Jeff , Scott Russell , Wilson Dennis , Moses Robert
Published: March 2007

OBJECTIVE—To investigate the efficacy and safety of acarbose as add-on therapy in overweight type 2 patients with diabetes inadequately controlled by metformin.

RESEARCH DESIGN AND METHODS—This study adopted a multicenter, randomized, double-blind, placebo-controlled, parallel group design. After a 4-week placebo run-in period, subjects were randomized to either acarbose (titrated up to 100 mg b.i.d.) or placebo. The primary efficacy variable was the change in HbA1c from baseline to the end of the 24-week treatment period. Change in fasting blood glucose was assessed as a secondary efficacy parameter.

RESULTS—The intention-to-treat analysis from baseline to week 24 (81 patients for HbA1c and 82 for fasting blood glucose) showed statistically significant differences between acarbose and placebo treatment in HbA1c (1.02%; 95% CI 0.543–1.497; P = 0.0001) and fasting blood glucose (1.132 mmol/l; 95% CI 0.056–2.208; P = 0.0395) (adjusted least square means). In all, 18 patients (47%) in the acarbose group were classified as responders with a ≥5% reduction in HbA1c (relative to baseline) at the end point compared to 6 (14%) in the placebo group (P = 0.001). The safety profiles were similar for both treatment groups except for the higher incidence of gastrointestinal side effects during acarbose therapy.

CONCLUSIONS—The addition of acarbose to metformin monotherapy provides an efficacious and safe alternative for glycemic improvement in overweight type 2 patients inadequately controlled by metformin alone.
Sildenafil Citrate for Treatment of Erectile Dysfunction in Men With Type 1 Diabetes
Authors: Stuckey Bronwyn G.A. , Jadzinsky Mauricio N. , Murphy Liam J. , Montorsi Francesco , Kadioglu Ates , Fraige Fadlo , Manzano Pilar , Deerochanawong Chaicharn
Published: March 2007

OBJECTIVE—In the 5–10% of diabetic men with type 1 diabetes, erectile dysfunction (ED) may be a particularly common and unwanted complication. This is the first study focusing exclusively on the effects of sildenafil in men with type 1 diabetes and ED.

RESEARCH DESIGN AND METHODS—A total of 188 patients were entered into a double-blind, placebo-controlled, parallel-group, flexible-dose study and were randomized to receive sildenafil (25–100 mg; n = 95) or placebo (n = 93) for 12 weeks. Efficacy was evaluated using questions three (Q3; achieving an erection) and four (Q4; maintaining an erection) from the International Index of Erectile Function (IIEF), a global efficacy question (GEQ; “Did treatment improve your erections?”), and a patient event log of sexual activity.

RESULTS—Improvements in mean scores from baseline to end-of-treatment for IIEF Q3 (35.7 vs. 19.9%) and Q4 (68.4 vs. 26.5%) were significant in patients receiving sildenafil compared with those receiving placebo (P = 0.0001). Moreover, the percent of improved erections (GEQ, 66.6 vs. 28.6%) and successful intercourse attempts (63 vs. 33%) was significantly increased with sildenafil compared with placebo. Improvements in sexual function were seen irrespective of the degree of ED severity. Adverse events were generally mild to moderate in severity, with headache (20 vs. 8%), flushing (18 vs. 3%), and dyspepsia (8 vs. 1%) reported more often in the sildenafil than in placebo-treated patients.

CONCLUSIONS—Treatment with sildenafil for ED was effective, resulting in an increased percentage of successful attempts at intercourse, and was well tolerated among men with type 1 diabetes.
Diagnostic Strategies to Detect Glucose Intolerance in a Multiethnic Population
Authors: Anand Sonia S. , Razak Fahad , Vuksan Vlad , Gerstein Hertzel C. , Malmberg Klas , Yi Qilong , Teo Koon K. , Yusuf Salim
Published: March 2007

OBJECTIVE—Identifying individuals who have elevated glucose concentrations is important for clinicians so that preventive strategies can be invoked, and it is useful for researchers who study associations between elevated glucose and adverse health outcomes. These methods should be applicable worldwide across different ethnic groups. Therefore, the objective of our analysis was to determine whether using the fasting glucose and HbA1c together could improve the classification of individuals with impaired glucose tolerance and diabetes in a multiethnic cohort randomly assembled in Canada.

RESEARCH DESIGN AND METHODS—We determined the optimum diagnostic criteria to identify people with abnormal glucose tolerance using fasting plasma glucose, 2-h post-glucose load plasma glucose, and HbA1c in 936 Canadians of South Asian, Chinese, and European descent.

RESULTS—The sensitivity of the American Diabetes Association (ADA) criteria to diagnose diabetes compared with the World Health Organization definitions was poor at 48.3% (95% confidence interval [CI] 35.7–61.0). Using a receiver operator characteristic curve, the optimum combined cut-point using fasting glucose and HbA1c to diagnose diabetes was a fasting glucose ≥5.7 mmol/l and an HbA1c ≥5.9%. These cut-points were associated with a sensitivity and specificity of 71.7% (60.3–83.1) and 95.0% (93.5–96.4), respectively, a positive likelihood ratio (LR) of 14.3 (9.6–19.0), and a negative LR of 0.3 (0.2–0.4). Significant ethnic variation in the sensitivity and specificity of this approach was observed: 47.4% (24.9–69.8) and 97.6% (95.9–99.4) among Europeans, 78.6% (57.1–100) and 95.9% (93.6–98.2) among Chinese, and 85.2% (71.8–98.6) and 91.3% (88.1–94.6) among South Asians, respectively. Participants with impaired glucose tolerance could not be identified reliably using the fasting glucose or HbA1c alone or in combination.

CONCLUSIONS—The sensitivity of the ADA criteria to diagnose diabetes is low, and there is substantial variation between ethnic groups. Fasting glucose and HbA1c may be used together to improve the identification of individuals who have diabetes, allowing clinicians to streamline the use of the oral glucose tolerance test.
Gestational Diabetes Mellitus
Authors: Daniells Suzie , Grenyer Brin F. S. , Davis Warren S. , Coleman Keith J. , Burgess Julie-Anne P. , Moses Robert G.
Published: March 2007

OBJECTIVE—To examine anxiety levels of women diagnosed with gestational diabetes mellitus (GDM) and to compare these with glucose-tolerant (GT) women at similar stages of pregnancy.

RESEARCH DESIGN AND METHODS—Prospective longitudinal study conducted on 50 women with GDM and 50 GT women. All women completed the Mental Health Inventory (MHI-5) forms and the Speilberger State-Trait Anxiety Inventory (STAI) at the beginning of the third trimester, antepartum, and 6 weeks postpartum. Specific questions were also assessed using a Likert scale.

RESULTS—Women with GDM, compared with GT women, had a higher level of anxiety (state rather than trait) at the time of the first assessment. However, before delivery and in the postpartum period, there were no significant differences in anxiety scores between the two groups. Women in both groups were positive about being tested for GDM and wished to be tested during future pregnancies.

CONCLUSIONS—There were no sustained increased levels of anxiety for women diagnosed with GDM. Concerns expressed about causing sustained maternal anxiety by testing for GDM could not be substantiated.
Pulse Wave Velocity as an Indicator of Atherosclerosis in Impaired Fasting Glucose
Authors: Ohnishi Hirofumi , Saitoh Shigeyuki , Takagi Satoru , Ohata Jun-ichi , Isobe Takeshi , Kikuchi Yuka , Takeuchi Hiroshi , Shimamoto Kazuaki
Published: March 2007

OBJECTIVE—Brachial-ankle pulse wave velocity (baPWV), as an indicator of atherosclerosis in impaired fasting glucose (IFG), was studied in 232 subjects randomly selected from inhabitants of two rural communities in Japan.

RESEARCH DESIGN AND METHODS—BMI, systolic blood pressure (SBP), fasting blood glucose (FBS), lipid parameters, ankle brachial pressure index (ABI), and baPWV were measured in each subject. ABI and baPWV were measured using the recently developed device, form ABI/PWV. The subjects were divided into three groups according FBS level: a normal group consisting of subjects with FBS <110 mg/dl, an IFG group consisting of subjects with FBS 110–125 mg/dl, and a diabetic group consisting of subjects with FBS ≥126 mg/dl and subjects taking hypoglycemic agents. The parameters in the three groups were compared.

RESULTS—It was found that the baPWV value increased with increasing plasma glucose level. Significant differences were found between the baPWV values in the normal and IFG groups (1,518 vs. 1,673 cm/s, P = 0.01) and in the normal and diabetic groups (1,518 vs. 1,771 cm/s, P < 0.0001). The results of multiple regression analysis showed that FBS was closely related to baPWV as well as to age and SBP.

CONCLUSIONS—The relationship between IFG and atherosclerosis remains controversial. Further studies are needed to evaluate whether strict control of blood glucose level in patients with IFG will result in the prevention of atherosclerosis progression.
Similar Genetic Features and Different Islet Cell Autoantibody Pattern of Latent Autoimmune Diabetes in Adults (LADA) Compared With Adult-Onset Type 1 Diabetes With Rapid Progression
Authors: Hosszúfalusi Nóra , Vatay Ágnes , Rajczy Katalin , Prohászka Zoltán , Pozsonyi Éva , Horváth Laura , Grosz Andrea , Gerõ László , Madácsy László , Romics László , Karádi István , Füst George , Pánczél Pál
Published: March 2007

OBJECTIVE—To compare the clinical parameters, C-peptide levels, pattern of islet cell-specific autoantibodies, and prevalence of predisposing genotypes in subjects with latent autoimmune diabetes in adults (LADA) and those with adult-onset type 1 diabetes with rapid progression.

RESEARCH DESIGN AND METHODS—We evaluated the clinical parameters, C-peptide levels, and islet cell-specific autoantibodies in 54 LADA, 57 adult-onset type 1 diabetic, and 190 type 2 diabetic patients. Islet cell autoantibodies were also compared between subgroups of newly diagnosed patients with LADA and those with newly diagnosed adult-onset and childhood-onset type 1 diabetes. The genetic study was performed in subjects with LADA and those with adult-onset type 1 diabetes in comparison with a control population.

RESULTS—There were no differences in the clinical parameters between LADA and adult-onset type 1 diabetes. Patients with LADA had lower BMI (P < 0.0001), waist-to-hip ratio (0.0029), total cholesterol (P = 0.001), and triglycerides (P = 0.001); higher HDL cholesterol levels (P < 0.0001); and lower prevalence of hypertension (P = 0.0028) compared with patients with type 2 diabetes. C-peptide levels were similar at onset (P = 0.403) but decreased less rapidly in LADA than in adult-onset type 1 diabetes (P = 0.0253). Single-autoantibody positivity was more often seen in LADA than in type 1 diabetes (P = 0.0001). The prevalence of predisposing HLA-DQB1*0302, -DR4, -DR3, and -DR3/DR4 genotypes and the DR4-DQB1*0302 haplotype were increased in both LADA and adult-onset type 1 diabetic subjects compared with the control population. There were no differences in the frequencies of these risk alleles and haplotypes between the two patient groups.

CONCLUSIONS—Subjects with LADA had clinical characteristics similar to those with adult-onset type 1 diabetes with rapid progression. C-peptide levels did not differ at onset but decreased less rapidly in LADA. Patients with LADA rather had single islet cell-specific autoantibody positivity. The prevalence of HLA-DQB1*0302, -DR4, -DR3, and -DR3/DR4 risk alleles and the DR4-DQB1*0302 high-risk haplotype did not differ in the two forms of autoimmune diabetes.
Clinical Performance of CGMS in Type 1 Diabetic Patients Treated by Continuous Subcutaneous Insulin Infusion Using Insulin Analogs
Authors: Guerci Bruno , Floriot Michèle , Böhme Philip , Durain Danielle , Benichou Muriel , Jellimann Stéphanie , Drouin Pierre
Published: March 2007

OBJECTIVE—Performance criteria have been established for in vitro blood glucose monitoring, particularly for the self-monitoring of blood glucose using glucose meters. Devices intended for use in the future, such as the continuous glucose monitoring system (CGMS), should satisfy similar criteria, particularly in diabetic patients under intensive therapy.

RESEARCH DESIGN AND METHODS—The analysis was conducted on 18 type 1 diabetic patients (not controlled, HbA1c >7.5%) treated by external pump using insulin analogs. Each patient received a glucose sensor for 3 days during his/her hospitalization and was instructed in its operation. Medtronic criteria were used to determine the accuracy of the CGMS. In addition, the data were analyzed according to American Diabetes Association (ADA) criteria, Clarke Error Grid analysis, and method of residuals, with the glucose oxidase method using a Beckman analyzer used as the reference method. Specificity and sensitivity were evaluated from the viewpoint of accuracy in the detection of hypoglycemia. For nine patients, two glucose sensors were simultaneously inserted into an abdominal site to determine the reproducibility of the system.

RESULTS—Among the 33 glucose sensors inserted, 6 (18%) were nonfunctional. The mean duration of CGMS recording was 63 ± 12 h. From all of the 692 sets of data that paired glucose readings and CGMS, the coefficients of correlation ranged from 0.87 to 0.92 and the mean absolute error ranged from 12.8 to 15.7%. The time experienced in hypoglycemia (<55 mg/dl) was reported at 86 ± 62 min/day. Only 39% of the CGMS values satisfied the ADA precision criteria to within ±10%, and 19% of these values satisfied the future ADA precision criteria of accuracy to within ±5%. The means of difference method showed that the CGMS slightly underestimated the plasma glucose values (mean = −12 mg/dl). Error grid analysis showed only 77% of the glucose sensor values were in zone A, and 98.9% were in zones A and B. Two values fell in zone C and a single value fell in zone D. The sensitivity and specificity of the CGMS to detect hypoglycemia were 33 and 96%, respectively. A total of 6,666 paired sensor values were recorded with a coefficient of correlation of 0.84 with a coefficient of variation of 8.25%.

CONCLUSIONS—CGMS could be useful in routine clinical practice to provide much more information on the glucose profile than intermittent self-monitoring of blood glucose (SMBG). However, CGMS cannot be used as a replacement for glucose meters because it does not satisfy the conventional performance goals set down for in vitro glucose measurements and could therefore lead to clinically incorrect treatment decisions.
Dietary Fat Predicts Coronary Heart Disease Events in Subjects With Type 2 Diabetes
Authors: Soinio Minna , Laakso Markku , Lehto Seppo , Hakala Paula , Rönnemaa Tapani
Published: March 2007

OBJECTIVE—To investigate whether quantity or quality of dietary fat predicts coronary heart disease (CHD) events in middle-aged type 2 diabetic subjects.

RESEARCH DESIGN AND METHODS—The dietary habits of 366 type 2 diabetic men and 295 women, aged 45–64 years and free from CHD, were assessed with a 53-item food frequency questionnaire. They were followed up for 7 years.

RESULTS—Men in the highest tertile of the polyunsaturated/saturated fat (P/S) ratio (>0.28) had a significantly lower risk for CHD death than men in the two lowest tertiles (5.0 vs. 14.2%, P = 0.009). The risk for all CHD events was 14.2 vs. 23.2%, respectively (P = 0.044). P/S ratio did not predict CHD events in women. In Cox multiple regression analyses taking into account other cardiovascular risk factors, the highest P/S ratio tertile was associated with the lowest rate of CHD death in men (P = 0.048).

CONCLUSIONS—Low P/S ratio in men predicted future CHD events in type 2 diabetic subjects independently of conventional CHD risk factors.
The Association Between Impaired Glucose Tolerance and Birth Weight Among Black and White Women in Central North Carolina
Authors: Saldana Tina M. , Siega-Riz Anna Maria , Adair Linda S. , Savitz David A. , Thorp John M.
Published: March 2007

OBJECTIVE—This study examines the relationship of glucose intolerance during pregnancy to birth weight among black and white participants of the Pregnancy, Infection, and Nutrition Study.

RESEARCH DESIGN AND METHODS—This prospective cohort study recruited women from prenatal clinics in central North Carolina at 24–29 weeks’ gestation. A 1-h 50-g glucose challenge test (GCT) and 100-g oral glucose tolerance test (OGTT) were conducted. Impaired glucose tolerance (IGT) was defined as one high value on the OGTT, gestational diabetes mellitus (GDM) as two or more high values, and normal glucose tolerance (NGT) was defined as a low or high value on the GCT screen but no high values on the OGTT. Women with known glucose status and birth outcome information were included in this analysis (n = 2055).

RESULTS—Black women with IGT had higher rates of both macrosomia (38.5%) and large for gestational age (LGA) (53.9%) compared with white women (10.0% and 13.2%). Black infants’ birth weights (3,800 g) and prevalence of macrosomia and LGA were significantly higher among mothers with IGT compared with NGT women (birth weight, 3,184 g; macrosomia, 7.0%; LGA, 11.6%). In contrast, among white infants, there was no significant increase in birth weight, macrosomia, or LGA associated with the mother’s glucose tolerance status. In addition, there was no effect of GDM on birth weight in either group.

CONCLUSIONS—This study suggests that, independent of maternal prepregnant weight, there may be significant increased risk of macrosomia among black IGT women but not among white IGT women. Further investigations into factors that may contribute to the observed results are needed.
Hypoglycemia Prevalence in Prepubertal Children With Type 1 Diabetes on Standard Insulin Regimen: Use of Continuous Glucose Monitoring System
Authors: Amin Rakesh , Ross Karen , Acerini Carlo L. , Edge Julie A. , Warner Justin , Dunger David B.
Published: March 2007

OBJECTIVE—To determine hypoglycemia prevalence in prepubertal children on thrice (TID) and twice (BID) daily insulin regimens, using the Medtronic Minimed Continuous Glucose Monitoring System.

RESEARCH DESIGN AND METHODS—Twenty-eight children aged <12 years (median 9.8, range 6.9–11.8) wore the sensor for three consecutive days and nights. Hypoglycemia was defined as glucose <60 mg/dl for >15 min. Data are expressed as the percentage of time period spent hypoglycemic.

RESULTS—Hypoglycemia prevalence was 10.1% (mean 2.6 h · subject−1 · day−1). Hypoglycemia was more common at night compared with daytime (18.81 vs. 4.4%, P < 0.001); 78 and 43% of subjects showed hypoglycemia on at least one night and two or more nights, respectively. Nocturnal episodes were prolonged (median 3.3 h) and asymptomatic (91% of episodes). Prevalence was greater between 0400 and 0730 h than between 2200 and 0400 h (25.5 vs. 15.4%, P < 0.001). On a TID compared with a BID regimen, nocturnal hypoglycemia prevalence was reduced, particularly between 0400–0730 h (22.9 vs. 27.4%, P = 0.005), whereas hypoglycemia the following morning (0730–1200 h) was greater (7.8 vs. 2.8%, P < 0.001). Nocturnal hypoglycemia risk was associated with decreasing age (by a factor of 0.6 for a year less in age), increased insulin dose (by 1.6 for an increase of 0.1 units · kg−1 · day−1), insulin regimen (by 0.2 on a BID compared with a TID regimen), and increased weight standard deviation score (SDS) (by 2.7 for a one SDS rise).

CONCLUSIONS—Use of standard insulin regimens results in high prevalence and large intraindividual variation in hypoglycemia, particularly at night. Independent risk factors for nocturnal hypoglycemia were younger age, greater daily insulin dose, insulin regimen, and increasing weight.
The Impact of Smoking on Inhaled Insulin
Authors: Himmelmann Anders , Jendle Johan , Mellén Anders , Petersen Astrid H. , Dahl Ulf L. , Wollmer Per
Published: March 2007

OBJECTIVE—This study, one of the first to address issues of pulmonary insulin delivery in smokers, compared pharmacokinetics of inhaled insulin delivered via the AERx insulin Diabetes Management System (iDMS) in nondiabetic cigarette smokers and nonsmokers.

RESEARCH DESIGN AND METHODS—In this randomized two-period crossover efficacy and safety trial in 27 nondiabetic smokers and 16 nonsmokers (18 men/25 women, mean age 28 years, mean BMI 23.0 kg/m2), subjects received single doses of inhaled insulin (33.8 IU) following overnight fasting on consecutive dosing days. On one dosing day, smokers smoked three cigarettes immediately before insulin administration (“acute smoking”); on the other dosing day, smokers had not smoked since midnight (“nonacute smoking”). After inhalation, 6-h serum insulin and serum glucose profiles were determined.

RESULTS—Pharmacokinetic results for evaluable subjects were derived from serum insulin profiles. The amount of insulin absorbed during the first 6 h after dosing (area under the exogenous serum insulin curve from 0 to 6 h [AUC(0–6 h)]) was significantly greater in smokers (63.2 vs. 40.0 mU · l−1 · h−1, P = 0.0017); peak concentration was both higher and earlier in the smokers (maximal serum concentration of insulin [Cmax] 42.0 vs. 13.9 mU/l, P < 0.0001; time to maximal serum concentration of insulin [tmax] 31.5 vs. 53.9 min, P = 0.0003). The estimated intrasubject variability of AUC(0–6 h) was 13.7 and 16.5% for nonsmokers and smokers, respectively. No safety issues arose.

CONCLUSIONS—Absorption of inhaled insulin via the AERx iDMS was significantly greater in smokers, with a higher AUC(0–6 h) and Cmax and a shorter tmax. Intrasubject variability of AUC(0–6 h) was low and similar in nonsmokers and smokers. These data prompt more extensive investigation of inhaled insulin in diabetic smokers.
Are Spouses of Patients With Type 2 Diabetes at Increased Risk of Developing Diabetes?
Authors: Khan Asya , Lasker Shawarna S. , Chowdhury Tahseen A.
Published: March 2007

OBJECTIVE—To determine whether spouses of patients with type 2 diabetes have an increased risk of diabetes compared with spouses of subjects with normal glucose tolerance.

RESEARCH DESIGN AND METHODS—A random sample of spouses of patients with type 2 diabetes (group 1S) attending a general practice diabetes clinic was compared with spouses of nondiabetic subjects (as determined by oral glucose tolerance test [OGTT]) (group 2S). Spouses in both groups underwent OGTT, fasting lipid profile, and blood pressure (BP) measurements.

RESULTS—A total of 245 subjects in group 1S and 234 subjects in group 2S underwent OGTT. Group 1S had a significantly higher incidence of fasting glucose, impaired glucose tolerance, or type 2 diabetes (19.1 vs. 9.4%). Group 1S also had higher fasting glucose and triglyceride levels, higher BMI, and a trend toward higher BP. Multivariate logistic regression analysis, adjusted for BMI and age, showed the risk of diabetes in the spouse of a patient with diabetes was 2.11 (95% CI 1.74–5.1), as compared with the spouse of a subject with normal glucose tolerance. Similarly, the risk of any degree of glucose intolerance in a spouse of a patient with type 2 diabetes was 2.32 (1.87–3.98), as compared with a spouse of a subject with normal glucose tolerance.

CONCLUSIONS—Spouses of patients with type 2 diabetes have a significantly increased risk of glucose intolerance and type 2 diabetes, and they should be classified as high risk for diabetes. This finding has implications for screening programs, which should include spouses of subjects with diabetes.
Unadjusted and Adjusted Prevalence of Diagnosed Depression in Type 2 Diabetes
Authors: Nichols Gregory A. , Brown Jonathan B.
Published: March 2007

OBJECTIVE—To estimate the prevalence of diagnosed depression in a large population of individuals with type 2 diabetes, compared to a matched control group, and to estimate the extent of depression that is independently associated with diabetes.

RESEARCH DESIGN AND METHODS—We compared the prevalence of diagnosed depression in all 16,180 full-year health maintenance organization members in 1999 who had been diagnosed with type 2 diabetes and in 16,180 comparison members without diabetes matched for age and sex. We ascertained diagnoses from the Kaiser Permanente Northwest Region’s electronic medical record. Using multiple logistic regression, we adjusted the prevalence estimates for the presence of cardiovascular disease, age, sex, and body weight.

RESULTS—Depression was more common in individuals with type 2 diabetes than among matched control subjects (17.9 vs. 11.2%; P < 0.001). Women in both groups were nearly twice as likely to be depressed as men; however, the relative difference in depression prevalence between subjects with and without diabetes was greater in men. In the multivariate model for women, body weight was a much stronger predictor of depression than diabetes status.

CONCLUSIONS—This study further documents the association between depression and diabetes, providing unadjusted population-based estimates in a large sample. Depression remained associated with diabetes after adjustment for several other possible causes. The association among diabetes, cardiovascular disease, depression, and obesity are multifaceted and differ for men and women.
Inhaled Insulin Using the AERx Insulin Diabetes Management System in Healthy and Asthmatic Subjects
Authors: Henry Robert R. , Mudaliar Sunder R.D. , Howland III William C. , Chu Neelima , Kim Dennis , An Bob , Reinhardt Rickey R.
Published: March 2007

OBJECTIVE—The AERx insulin Diabetes Management System (AERx iDMS) (Aradigm, Hayward, CA) delivers an aerosol of liquid human insulin to the deep lung for systemic absorption. This study examined the effects on pulmonary function, pharmacokinetics, and pharmacodynamics of inhaled insulin in asthmatic and nonasthmatic subjects without diabetes.

RESEARCH DESIGN AND METHODS—A total of 28 healthy and 17 asthmatic (forced expiratory volume during the first second [ FEV1] 50–80% of predicted value) subjects were enrolled in a two-part, open-label trial. To assess insulin pharmacokinetics and pharmacodynamics, a single inhalation dose of 1.57 mg (45 IU) was given on each of the 2 dosing days in part 1. A dose of 4.7 mg (135 IU) of insulin was inhaled in part 2 to assess effects on pulmonary function.

RESULTS—Inhaled insulin showed area under the curve (AUC)(0–360 min) values that were significantly greater for healthy subjects than for asthmatic subjects (P = 0.013), whereas no difference was observed for maximum concentration (Cmax) in the two groups. A greater reduction of serum glucose as indicated by area over the curve (AOC)(0–360 min) was observed in healthy subjects (P = 0.007). Asthmatic subjects had greater intrasubject variations in insulin AUC(0–360 min) and Cmax values than healthy subjects, but similar variations in glucose AOC(0–360 min). No significant changes in FEV1, forced vital capacity (FVC), and FEV1/FVC were observed from pre- to postdose times, and there were no observed safety issues.

CONCLUSIONS—After inhaling insulin using the AERx iDMS, asthmatic subjects absorbed less insulin than healthy subjects, resulting in less reduction of serum glucose. No effects on airway reactivity were observed. Diabetic patients with asthma may need to inhale more insulin than patients with normal respiratory function in order to achieve similar glycemic control.
Differential Effects of Acute and Extended Infusions of Glucagon-Like Peptide-1 on First- and Second-Phase Insulin Secretion in Diabetic and Nondiabetic Humans
Authors: Quddusi Shaista , Vahl Torsten P. , Hanson Kevin , Prigeon Ronald L. , D’Alessio David A.
Published: March 2007

OBJECTIVE—The purpose of this study was to determine whether an extended infusion of the incretin hormone glucagon-like peptide 1 (GLP-1) has a greater effect to promote insulin secretion in type 2 diabetic subjects than acute administration of the peptide.

RESEARCH DESIGN AND METHODS—Nine diabetic subjects and nine nondiabetic volunteers of similar age and weight were studied in identical protocols. First-phase insulin release (FPIR; the incremental insulin response in the first 10 min after the intravenous glucose bolus) and second-phase insulin release (SPIR; the incremental insulin response from 10–60 min after intravenous glucose) were measured during three separate intravenous glucose tolerance tests (IVGTTs): 1) without GLP-1 (control); 2) with acute administration of GLP-1 as a square wave starting just before glucose administration; and 3) with an extended infusion of GLP-1 for 3 h before and during the IVGTT.

RESULTS—In the subjects with diabetes, FPIR was severely impaired—a defect that was only modestly improved by acute administration of GLP-1 (197 ± 97 vs. 539 ± 218 pmol/l · min, P < 0.05), while SPIR was substantially increased (1,952 ± 512 vs. 8,072 ± 1,664 pmol/l · min, P < 0.05). In contrast, the 3-h preinfusion of GLP-1 normalized fasting hyperglycemia (7.9 ± 0.5 vs. 5.2 ± 0.6, P < 0.05), increased FPIR by 5- to 6-fold (197 ± 97 vs. 1,141 ± 409 pmol/l · min, P < 0.05), and augmented SPIR significantly (1,952 ± 512 vs. 4,026 ± 851 pmol/l · min, P < 0.05), but to a lesser degree than the acute administration of GLP-1. In addition, only the 3-h GLP-1 preinfusion significantly improved intravenous glucose tolerance (Kg control 0.61 ± 0.04, acute infusion 0.71 ± 0.04, P = NS; 3-h infusion 0.92 ± 0.08%/min, P < 0.05). These findings were also noted in the nondiabetic subjects in whom acute administration of GLP-1 significantly increased SPIR relative to the control IVGTT (9,439 ± 2,885 vs. 31,553 ± 11660 pmol/l · min, P < 0.001) with less effect on FPIR (3,221 ± 918 vs. 4,917 ± 1,614 pmol/l · min, P = 0.075), while the 3-h preinfusion of GLP-1 significantly increased both FPIR (3,221 ± 918 vs. 7,948 ± 2,647 pmol/l · min, P < 0.01) and SPIR (9,439 ± 2,885 vs. 21,997 ± 9,849 pmol/l · min, P < 0.03).

CONCLUSIONS—Extended administration of GLP-1 not only augments glucose-stimulated insulin secretion, but also shifts the dynamics of the insulin response to earlier release in both diabetic and nondiabetic humans. The restitution of some FPIR in subjects with type 2 diabetes is associated with significantly improved glucose tolerance. These findings demonstrate the benefits of a 3-h infusion of GLP-1 on β-cell function beyond those of an acute insulin secretagogue, and support the development of strategies using continuous or prolonged GLP-1 receptor agonism for treating diabetic patients.