bluuebunny/crossref_metadata_2025 huggingface dataset:
An Endocrinologist-Supported Intervention Aimed at Providers Improves Diabetes Management in a Primary Care Site
Authors: Phillips Lawrence S. , Ziemer David C. , Doyle Joyce P. , Barnes Catherine S. , Kolm Paul , Branch William T. , Caudle Jane M. , Cook Curtiss B. , Dunbar Virginia G. , El-Kebbi Imad M. , Gallina Daniel L. , Hayes Risa P. , Miller Christopher D. , Rhee Mary K. , Thompson Dennis M. , Watkins Clyde
Published: March 2007

OBJECTIVE—Management of diabetes is frequently suboptimal in primary care settings, where providers often fail to intensify therapy when glucose levels are high, a problem known as clinical inertia. We asked whether interventions targeting clinical inertia can improve outcomes.

RESEARCH DESIGN AND METHODS—A controlled trial over a 3-year period was conducted in a municipal hospital primary care clinic in a large academic medical center. We studied all patients (4,138) with type 2 diabetes who were seen in continuity clinics by 345 internal medicine residents and were randomized to be control subjects or to receive one of three interventions. Instead of consultative advice, the interventions were hard copy computerized reminders that provided patient-specific recommendations for management at the time of each patient’s visit, individual face-to-face feedback on performance for 5 min every 2 weeks, or both.

RESULTS—Over an average patient follow-up of 15 months within the intervention site, improvements in and final HbA1c (A1C) with feedback + reminders (ΔA1C 0.6%, final A1C 7.46%) were significantly better than control (ΔA1C 0.2%, final A1C 7.84%, P < 0.02); changes were smaller with feedback only and reminders only (P = NS vs. control). Trends were similar but not significant with systolic blood pressure (sBP) and LDL cholesterol. Multivariable analysis showed that the feedback intervention independently facilitated attainment of American Diabetes Association goals for both A1C and sBP. Over a 2-year period, overall glycemic control improved in the intervention site but did not change in other primary care sites (final A1C 7.5 vs. 8.2%, P < 0.001).

CONCLUSIONS—Feedback on performance aimed at overcoming clinical inertia and given to internal medicine resident primary care providers improves glycemic control. Partnering generalists with diabetes specialists may be important to enhance diabetes management in other primary care settings.
Metabolic Control of Diabetes Is Associated With an Improved Response of Diabetic Retinopathy to Panretinal Photocoagulation
Authors: Kotoula Maria G. , Koukoulis George N. , Zintzaras Elias , Karabatsas Constantinos H. , Chatzoulis Dimitrios Z.
Published: March 2007

OBJECTIVE—To study the influence of glycemic control and the presence of microalbuminuria on the initial response to panretinal photocoagulation (PRP) in patients with a high-risk proliferative diabetic retinopathy (PDR).

RESEARCH DESIGN AND METHODS—This was a prospective cohort study with a two-by-two factorial design. We used full-scattered PRP to treat 115 eyes of type 2 diabetic patients who have high-risk PDR. HbA1c (A1C) and albumin levels in 24-h urine were constantly monitored during the preenrollment, treatment, and posttreatment periods. At a follow-up visit 12 weeks after the last PRP session, the fundus was examined for characteristics of regression from high-risk PDR and the response to PRP was determined to be successful or unsuccessful. The eyes were categorized into four groups based on average A1C levels and the presence or absence of microalbuminuria. The data were analyzed using a logistic regression model. Our statistical analysis determined the probability of achieving a satisfactory response to PRP in association with A1C levels and the presence or absence of microalbuminuria.

RESULTS—Of the 115 eyes examined, 65 (56.5%) had a successful initial response to PRP and 50 (43.5%) did not. The probability of a satisfactory response to PRP was related to A1C levels (P < 0.05) but not to microalbuminuria and its interaction with hemoglobin glycosylation (P ≥ 0.05).

CONCLUSIONS—Low levels of hemoglobin glycosylation (A1C <8%) during the pretreatment, treatment, and posttreatment periods are associated with a regression of proliferative diabetic retinopathy after PRP.
Comparison of the Effects of Vitamins and/or Mineral Supplementation on Glomerular and Tubular Dysfunction in Type 2 Diabetes
Authors: Farvid Maryam Sadat , Jalali Mahmoud , Siassi Fereydoun , Hosseini Mostafa
Published: March 2007

OBJECTIVE—The present study was designed to assess the effect of magnesium plus zinc, vitamins C plus E, and a combination of these micronutrients on nephropathy indexes in type 2 diabetic patients.

RESEARCH DESIGN AND METHODS—In a randomized, double-blind, placebo-controlled clinical trial, 69 type 2 diabetic patients were randomly divided into four groups, each group receiving one of the following daily supplement for 3 months: group M (n = 16), 200 mg Mg and 30 mg Zn; group V (n = 18), 200 mg vitamin C and 100 IU vitamin E; group MV (n = 17), minerals plus vitamins; and group P (n = 18), placebo. Urinary albumin excretion and N-acetyl-β-d-glucosaminidase activity (NAG) in urine were determined at the beginning and at the end of the trial. Treatment effects were analyzed by general linear modeling.

RESULTS—Results indicate that after 3 months of supplementation, levels of urinary albumin excretion decreased in the V and MV groups (P = 0.034 and P = 0.005, respectively). Urinary NAG activity did not significantly change in any treatment groups. Levels of systolic, diastolic, and mean blood pressure significantly decreased in the MV group (P = 0.008, P = 0.017, and P = 0.009, respectively). Also, combination of vitamin and mineral supplementation had significant effects in decreasing fasting serum glucose (P = 0.035) and malondialdehyde concentrations (P = 0.004) and in increasing HDL cholesterol and apolipoprotein A1 levels (P = 0.019). There was no significant change in the levels of these parameters in the other three groups.

CONCLUSIONS—In conclusion, the results of the present study provide evidence for the effects of vitamins C and E and also combination of magnesium, zinc, and vitamins C and E supplementation on improvement of glomerular but not tubular renal function in type 2 diabetic patients.
Diabetes During Diarrhea-Associated Hemolytic Uremic Syndrome
Authors: Suri Rita S. , Clark William F. , Barrowman Nick , Mahon Jeffrey L. , Thiessen-Philbrook Heather R. , Rosas-Arellano M. Patricia , Zarnke Kelly , Garland Jocelyn S. , Garg Amit X.
Published: March 2007

OBJECTIVE—To quantify the incidence of diabetes during the acute phase of diarrhea-associated hemolytic uremic syndrome (D+HUS) and to identify features associated with its development.

RESEARCH DESIGN AND METHODS—A systematic review and meta-analysis of articles assessing diabetes during D+HUS was conducted. Relevant citations were identified from Medline, Embase, and Institute for Scientific Information Citation Index databases. Bibliographies of relevant articles were hand searched. All articles were independently reviewed for inclusion and data abstraction by two authors.

RESULTS—Twenty-one studies from six countries were included. Only 2 studies reported a standard definition of diabetes; 14 defined diabetes as hyperglycemia requiring insulin. The incidence of diabetes during the acute phase of D+HUS could be quantified in a subset of 1,139 children from 13 studies (1966–1998, age 0.2–16 years) and ranged from 0 to 15%, with a pooled incidence of 3.2% (95% CI 1.3–5.1, random-effects model, significant heterogeneity among studies, P = 0.007). Children who developed diabetes were more likely to have severe disease (e.g., presence of coma or seizures, need for dialysis) and had higher mortality than those without diabetes. Twenty-three percent of those who developed diabetes acutely died, and 38% of survivors required long-term insulin (median follow-up 12 months). Recurrence of diabetes was possible up to 60 months after initial recovery.

CONCLUSIONS—Children with D+HUS should be observed for diabetes during their acute illness. Consideration should be given to long-term screening of D+HUS survivors for diabetes.
The Relation of Fasting and 2-h Postchallenge Plasma Glucose Concentrations to Mortality
Authors: Sorkin John D. , Muller Denis C. , Fleg Jerome L. , Andres Reubin
Published: March 2007

OBJECTIVE—Under the auspices of the National Institutes of Health, American Diabetes Association, and World Health Organization, expert committees lowered the fasting plasma glucose (FPG) concentration diagnostic for diabetes from 7.8 to 7.0 mmol/l and defined 6.1–6.9 mmol/l as impaired fasting glucose (IFG) and <6.1 mmol/l as normal fasting glucose. In 2003, IFG was lowered to 5.6–6.9 mmol/l and normal fasting glucose to <5.6 mmol/l. Reports of the relationship between glucose concentration and all-cause mortality have been inconsistent. It is not known if the 2-h plasma glucose (2hPG) concentration from an oral glucose tolerance test (OGTT) adds to the predictive power of FPG.

RESEARCH DESIGN AND METHODS—We followed 1,236 men for an average of 13.4 years to determine the relationship between both FPG and 2hPG and all-cause mortality.

RESULTS—Risk for mortality did not increase until the FPG exceeded 6.1 mmol/l. Risk increased by ∼40% in the 6.1–6.9 mmol/l range and doubled when FPG ranged from 7.0 to 7.7 mmol/l. A combination of the 2hPG and FPG allowed better estimation of risk than the FPG alone. Within any category of FPG, risk generally increased as the 2hPG increased, and within any category of 2hPG, risk generally increased as the FPG increased.

CONCLUSIONS—These data support the decision to lower the FPG diagnostic for diabetes from 7.8 to 7.0 mmol/l, show that both IFG and impaired glucose tolerance have risks between the normal and diabetic ranges, and show that the OGTT adds predictive power to that of FPG alone and should not be abandoned. The lowering of IFG to 5.6 mmol/l from 6.1 mmol/l, at least for mortality, is, however, not supported by our results.
Does Diabetes Care Compete With the Provision of Women’s Preventive Care Services?
Authors: Tabaei Bahman P. , Herman William H. , Jabarin Annissa F. , Kim Catherine
Published: March 2007

OBJECTIVE—Care for chronic diseases may compete with preventive health care. To test this hypothesis, we examined the association between diabetes-related processes of care and preventive care in women.

RESEARCH DESIGN AND METHODS—Using data from a prospective cohort study of diabetes care in managed care settings, we reviewed the care 540 diabetic women received from 355 primary care providers within 14 provider groups from one health plan. Of the 540 women, 278 were eligible to receive mammograms and 314 were eligible to receive Pap smears. Mammography performance was measured as at least one mammogram over a 2-year period and Pap performance was measured as at least one Pap smear over a 3-year period. To assess the association between diabetes-related processes of care and preventive services, we used hierarchical logistic regression models, accounted for clustering within provider groups, and adjusted for patient age, race, income and education level, diabetes treatment and duration, and health status, as well as physician age, sex, years of practice, and specialty. Diabetes-related processes of care were defined as dilated retinal examinations, urine microalbumin/protein testing, foot examinations, lipid and HbA1c testing, recommendations to take aspirin, and influenza vaccinations received over a 1-year period.

RESULTS—In this cohort, 73% of eligible women received mammograms and 56% received Pap smears. After adjustment of models, better diabetes-related processes of care, better health status, and non-Medicaid insurance were associated with mammography performance. Better diabetes-related processes of care, younger patient age, and any visit to a gynecologist were associated with Pap performance.

CONCLUSIONS—Better processes of diabetes care were associated with better women’s preventive health care. Diabetes management did not compete with sex-specific screening.
Postpartum Physical Activity and Related Psychosocial Factors Among Women With Recent Gestational Diabetes Mellitus
Authors: Smith Ben J. , Cheung N. Wah , Bauman Adrian E. , Zehle Katharina , McLean Mark
Published: March 2007

OBJECTIVE—In this study, we examined patterns of postpartum physical activity among women with recent gestational diabetes mellitus (GDM) and psychosocial factors related to this behavior that could be addressed in diabetes prevention interventions.

RESEARCH DESIGN AND METHODS—A random sample of women who had attended diabetes clinics in Sydney, Australia, in the past 6–24 months for treatment of GDM were surveyed by telephone. Variables measured included physical activity behaviors, self-efficacy, social support, and barriers to participation.

RESULTS—Of 226 women who completed the survey (mean age 33.4 years), 26.5% were classified as sedentary, and only 33.6% reported sufficient physical activity as recommended by health authorities. Walking was the most popular physical activity, and most women reported no other moderate- or vigorous-intensity activity. Lack of assistance with child care (49.1%) and insufficient time (37.6%) were the most common barriers to physical activity. The type of social support most often reported was verbal encouragement (39.1%), with more than half of the women never receiving assistance with housework or others exercising with them. Self-efficacy for physical activity was lowest when women were under time pressure or tired. Multivariate analyses showed that sufficient physical activity was associated with high social support (odds ratio 2.5 [95% CI 1.21–3.79]) and high self-efficacy (2.09 [1.06–3.20]).

CONCLUSIONS—The prevalence of sufficient physical activity was found to be low and strongly related to social support and self-efficacy. This is an important group to whom diabetes prevention strategies can be targeted.
Resistance to Insulin Therapy Among Patients and Providers
Authors: Peyrot Mark , Rubin Richard R. , Lauritzen Torsten , Skovlund Soren E. , Snoek Frank J. , Matthews David R. , Landgraf Rüdiger , Kleinebreil Line ,   on behalf of the International DAWN Advisory Panel
Published: March 2007

OBJECTIVE—To examine the correlates of patient and provider attitudes toward insulin therapy.

RESEARCH DESIGN AND METHODS—Data are from surveys of patients with type 2 diabetes not taking insulin (n = 2,061) and diabetes care providers (nurses = 1,109; physicians = 2,681) in 13 countries in Asia, Australia, Europe, and North America. Multiple regression analysis is used to identify correlates of attitudes toward insulin therapy among patients, physicians, and nurses.

RESULTS—Patient and provider attitudes differ significantly across countries, controlling for individual characteristics. Patients rate the clinical efficacy of insulin as low and would blame themselves if they had to start insulin therapy. Self-blame is significantly lower among those who have better diet and exercise adherence and less diabetes-related distress. Patients who are not managing their diabetes well (poor perceived control, more complications, and diabetes-related distress) are significantly more likely to see insulin therapy as potentially beneficial. Most nurses and general practitioners (50–55%) delay insulin therapy until absolutely necessary, but specialists and opinion leaders are less likely to do so. Delay of insulin therapy is significantly less likely when physicians and nurses see their patients as more adherent to medication or appointment regimens, view insulin as more efficacious, and when they are less likely to delay oral diabetes medications.

CONCLUSIONS—Patient and provider resistance to insulin therapy is substantial, and for providers it is part of a larger pattern of reluctance to prescribe blood glucose–lowering medication. Interventions to facilitate timely initiation of insulin therapy will need to address factors associated with this resistance.
Comparison of a Needle-Type and a Microdialysis Continuous Glucose Monitor in Type 1 Diabetic Patients
Authors: Wentholt Iris M. , Vollebregt Marit A. , Hart Augustus A. , Hoekstra Joost B. , DeVries J. Hans
Published: March 2007

OBJECTIVE—We examined the reliability of two continuous glucose sensors in type 1 diabetic patients at night and during rapid glucose excursions and verified the hypothesized nocturnal hypoglycemic drift of the needle-type sensor (CGMSgold) and delay of the microdialysis sensor (GlucoDay).

RESEARCH DESIGN AND METHODS—Blood was sampled overnight twice per hour in 13 patients. Rapid-acting insulin was given subcutaneously 30 min after breakfast. Sampling once per minute started 45 min after breakfast and 75 min after insulin injection for 30 min, with the aim of determining peak and nadir glucose values. Mean absolute differences (MADs) between sensor and blood glucose values were calculated. Sensor curves were modeled for all patients using linear regression. Horizontal and vertical shifts of sensor curves from the blood glucose curves were assessed. A vertical shift indicates sensor drift and a horizontal shift sensor delay.

RESULTS—Drift was minimal in the needle-type and microdialysis sensors (−0.02 and −0.04 mmol/l). Mean ± SD delay was 7.1 ± 5.5 min for the microdialysis sensor (P < 0.001). MAD was 15.0% for the needle-type sensor and 13.6% for the microdialysis sensor (P = 0.013). After correction for the 7-min delay, the microdialysis MAD improved to 11.7% (P < 0.0001).

CONCLUSIONS—The microdialysis sensor was more accurate than the needle-type sensor, with or without correction for a 7-min delay. In contrast to the previous version, the current needle-type sensor did not exhibit nocturnal hypoglycemic drift. Continuous subcutaneous glucose sensors are valuable adjunctive tools for glucose trend analyses. However, considering the large MADs, individual sensor values should be interpreted with caution.
Serum Interleukin-18 Levels Are Associated With Nephropathy and Atherosclerosis in Japanese Patients With Type 2 Diabetes
Authors: Nakamura Akihiko , Shikata Kenichi , Hiramatsu Makoto , Nakatou Tatsuaki , Kitamura Takuya , Wada Jun , Itoshima Tatsuya , Makino Hirofumi
Published: March 2007

OBJECTIVE—Interleukin (IL)-18 is a proinflammatory cytokine secreted from mononuclear cells. Serum concentration of IL-18 is a strong predictor of death in patients with cardiovascular diseases. Recent studies have shown that microinflammation is involved in the pathogenesis of diabetic nephropathy as well as of cardiovascular diseases. This study aimed to test the hypothesis that the serum level of IL-18 is a common predictor of nephropathy and atherosclerosis in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS—Eighty-two Japanese patients with type 2 diabetes and 55 age- and sex-matched healthy control subjects were enrolled. Patients with renal dysfunction (creatinine clearance <1 ml/s) were excluded. We assessed clinical parameters and measured serum and urinary IL-18 levels, serum IL-6 levels, carotid intima-media thickness (IMT), and brachial-ankle pulse wave velocity (baPWV) in all patients. Further, we evaluated changes of urinary albumin excretion rate (AER) after 6 months in 76 diabetic patients.

RESULTS—Serum and urinary IL-18 levels were significantly elevated in patients with type 2 diabetes as compared with control subjects (serum IL-18 179 ± 62 vs. 121 ± 55 pg/ml, P < 0.001; urinary IL-18 97 ± 159 vs. 47 ± 54 pg/ml, P = 0.035). Univariate linear regression analysis showed significant positive correlations between serum IL-18 and AER (r [correlation coefficient] = 0.525, P < 0.001), HbA1c (r = 0.242, P = 0.029), high-sensitivity C-reactive protein (hs-CRP) (r = 0.240, P = 0.031), and urinary β-2 microglobulin (r = 0.235, P = 0.036). Serum IL-18 levels also correlated positively with carotid IMT (r = 0.225, P = 0.042) and baPWV (r = 0.232, P = 0.040). We also found a significant correlation between urinary IL-18 and AER (r = 0.309, P = 0.005). Multivariate linear regression analysis showed that AER (standard correlation coefficients [B] = 0.405, P < 0.001) and hs-CRP (B = 0.207, P = 0.033) were independently associated with serum IL-18 levels. AER was also independently associated with urinary IL-18 levels (B = 0.295, P = 0.005). Moreover, serum and urinary IL-18 levels correlated positively with AER after 6 months (r = 0.489, P < 0.001 and r = 0.320, P = 0.005) and changes in AER during the follow-up period (r = 0.268, P = 0.018 and r = 0.234, P = 0.042).

CONCLUSIONS—Serum levels of IL-18 might be a predictor of progression of diabetic nephropathy as well as cardiovascular diseases.
Total Contact Casting of the Diabetic Foot in Daily Practice
Authors: Nabuurs-Franssen Marrigje H. , Sleegers Ron , Huijberts Maya SP , Wijnen Wiel , Sanders Antal P. , Walenkamp Geert , Schaper Nicolaas C.
Published: March 2007

OBJECTIVE— A limited number of clinical trials have shown that the total contact cast (TCC) is an effective treatment in neuropathic, noninfected, and nonischemic foot ulcers. In this prospective data collection study, we assessed outcome and complications of TCC treatment in neuropathic patients with and without peripheral arterial disease (PAD) or (superficial) infection.

RESEARCH DESIGN AND METHODS— Ninety-eight consecutive patients selected for casting were followed until healing; all had polyneuropathy, 44% had PAD, and 29% had infection. Primary outcomes were percentage healed with a cast, time to heal, and number of complications.

RESULTS— Ninety percent of all nonischemic ulcers without infection and 87% with infection healed in the cast (NS). In patients with PAD but without critical limb ischemia, 69% of the ulcers without infection and 36% with infection healed (P < 0.01). In multivariate analyses, PAD, infection, and heel ulcers were associated with a lower percentage healed (all P < 0.05). Median duration of cast treatment was 34 days. New ulcers, all superfical, developed in 9% and preulcerative lesions in 28% of the patients; these skin lesions healed in the cast within a maximum of 13 days.

CONCLUSIONS— In comparison to pure neuropathic ulcers, ulcers with moderate ischemia or infection can be treated effectively with casting. However, when both PAD and infection are present or the patient has a heel ulcer, outcome is poor and alternative strategies should be sought. The high rate of preulcerative lesions stresses the importance of close monitoring during TCC treatment.
Initiating Insulin Therapy in Type 2 Diabetes
Authors: Raskin Philip , Allen Elsie , Hollander Priscilla , Lewin Andrew , Gabbay Robert A. , Hu Peter , Bode Bruce , Garber Alan ,   for the INITIATE Study Group
Published: March 2007

OBJECTIVE—Safety and efficacy of biphasic insulin aspart 70/30 (BIAsp 70/30, prebreakfast and presupper) were compared with once-daily insulin glargine in type 2 diabetic subjects inadequately controlled on oral antidiabetic drugs (OADs).

RESEARCH DESIGN AND METHODS—This 28-week parallel-group study randomized 233 insulin-naive patients with HbA1c values ≥8.0% on >1,000 mg/day metformin alone or in combination with other OADs. Metformin was adjusted up to 2,550 mg/day before insulin therapy was initiated with 5–6 units BIAsp 70/30 twice daily or 10–12 units glargine at bedtime and titrated to target blood glucose (80–110 mg/dl) by algorithm-directed titration.

RESULTS—A total of 209 subjects completed the study. At study end, the mean HbA1c value was lower in the BIAsp 70/30 group than in the glargine group (6.91 ± 1.17 vs. 7.41 ± 1.24%, P < 0.01). The HbA1c reduction was greater in the BIAsp 70/30 group than in the glargine group (−2.79 ± 0.11 vs. −2.36 ± 0.11%, respectively; P < 0.01), especially for subjects with baseline HbA1c >8.5% (−3.13 ± 1.63 vs. −2.60 ± 1.50%, respectively; P < 0.05). More BIAsp 70/30–treated subjects reached target HbA1c values than glargine-treated subjects (HbA1c ≤6.5%: 42 vs. 28%, P < 0.05; HbA1c <7.0%: 66 vs. 40%, P < 0.001). Minor hypoglycemia (episodes/year) was greater in the BIAsp 70/30 group than in the glargine group (3.4 ± 6.6 and 0.7 ± 2.0, respectively; P < 0.05). Weight gain and daily insulin dose at study end were greater for BIAsp 70/30–treated subjects than for glargine-treated subjects (weight gain: 5.4 ± 4.8 vs. 3.5 ± 4.5 kg, P < 0.01; insulin dose: 78.5 ± 39.5 and 51.3 ± 26.7 units/day, respectively).

CONCLUSIONS—In subjects with type 2 diabetes poorly controlled on OADs, initiating insulin therapy with twice-daily BIAsp 70/30 was more effective in achieving HbA1c targets than once-daily glargine, especially in subjects with HbA1c >8.5%.
Prognostic Effect of Insertion/Deletion Polymorphism of the ACE Gene on Renal and Cardiovascular Clinical Outcomes in Chinese Patients With Type 2 Diabetes
Authors: Wang Ying , Ng Maggie C.Y. , So Wing Yee , Tong Peter C.Y. , Ma Ronald C.W. , Chow Chun Chung , Cockram Clive S. , Chan Juliana C.N.
Published: March 2007

OBJECTIVE— The insertion/deletion (I/D) polymorphism of the ACE gene has been reported to be associated with diabetic microvascular or macrovascular complications. The aim of the present study was to investigate the prognostic effect of I/D polymorphism on renal and cardiovascular clinical outcomes in Chinese patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS— A consecutive cohort of 1,281 Chinese patients with type 2 diabetes were followed for 41.3 ± 21.6 months. Renal end points were defined as renal death and events (need for dialysis, plasma creatinine ≥500 μmol/l, or doubling of plasma creatinine of baseline value ≥150 μmol/l). Cardiovascular end points were defined as cardiovascular death and events, which included ischemic heart disease, heart failure, cerebrovascular accident, and revascularization requiring hospital admission. The I/D polymorphism of the ACE gene was examined by PCR followed by agarose gel electrophoresis.

RESULTS— The frequencies of ACE gene I/D polymorphisms were in Hardy-Weinberg equilibrium. Patients who developed a renal end point (n = 98) had higher frequencies of DD genotype (19.4 vs. 10.8%, P = 0.018) and D allele (41.3 vs. 31.8%, P = 0.006) compared with subjects who did not (n = 1,183). The cumulative rates of renal end points were 10.0, 19.2, and 24.4% in the II (n = 595), DI (n = 539), and DD genotype carriers (n = 147), respectively (log rank P = 0.004). In multiple Cox regression analysis, the occurrence of renal end points remained significantly influenced by I/D polymorphism with a dominant deleterious effect of the DD genotype (DD versus II, adjusted hazard ratio 2.80 [95% CI 1.49–5.29]). There was no prognostic effect of I/D polymorphism on cardiovascular end points.

CONCLUSIONS— The DD genotype of the ACE I/D polymorphism was an independent risk factor for renal but not cardiovascular end points in Chinese patients with type 2 diabetes.
Repaglinide Administration Improves Brachial Reactivity in Type 2 Diabetic Patients
Authors: Manzella Daniela , Grella Rodolfo , Abbatecola Angela Marie , Paolisso Giuseppe
Published: March 2007

OBJECTIVE—Several studies have demonstrated that endothelial dysfunction plays a central role in diabetic mortality and that the prooxidative effect of postprandial hyperglycemia may actively contribute to atherogenesis. Thus, we investigated the possible effect of short-acting (repaglinide) and long-acting (glibenclamide) insulin secretagogues on endothelial function in type 2 diabetic patients.

RESEARCH DESIGN AND METHODS—Sixteen type 2 diabetic patients undergoing diet treatment and with poor glucose control volunteered for the study. The study was designed as a 4-month, randomized, cross-over, parallel-group trial of repaglinide (1 mg twice a day) versus glibenclamide (5 mg twice a day). All patients underwent the following investigations: 1) anthropometrics determinations, 2) blood sampling for routine laboratory analyses and for assessment of oxidative stress indexes, and 3) a brachial reactivity test to evaluate the endothelial function through the study of arterial diameter and flow changes with and without intraarterial infusion of NG-monomethyl-l-arginine, an inhibitor of nitric oxide synthase and tetraethylammonium chloride (TEA), a Ca2+-activated K+ (KCa) channel blocker. All patients were randomly assigned to receive repaglinide or glibenclamide for a period of 4 weeks.

RESULTS—Repaglinide administration was associated with a significant reduction in 2-h plasma glucose levels (P < 0.001) and in plasma thiobarbituric acid–reactive substances (TBARS) concentrations (P < 0.001) and with a significant increase in plasma antioxidant power, assessed as Trolox equivalent antioxidant capacity (TEAC) (P < 0.001), effects not observed after glibenclamide administration. With regard to brachial reactivity parameters, repaglinide but not glibenclamide was associated with a significant improvement in brachial reactivity parameters (P < 0.003 for all parameters). In contrast, intra-arterial infusion ofl-NMMA and TEA reduced the beneficial effect of repaglinide.

CONCLUSIONS—Repaglinide administration, through good control of postprandial glucose levels, improves brachial reactivity and declines oxidative stress indexes.
The Metabolic Syndrome and 11-Year Risk of Incident Cardiovascular Disease in the Atherosclerosis Risk in Communities Study
Authors: McNeill Ann Marie , Rosamond Wayne D. , Girman Cynthia J. , Golden Sherita Hill , Schmidt Maria I. , East Honey E. , Ballantyne Christie M. , Heiss Gerardo
Published: March 2007

OBJECTIVE— To assess the magnitude of the association between the National Cholesterol Education Program’s Third Adult Treatment Panel Report (ATP III) definition of the metabolic syndrome and cardiovascular disease (CVD).

RESEARCH DESIGN AND METHODS— Cox regression was used to estimate the relative risk of incident coronary heart disease (CHD) and stroke among 12,089 black and white middle-aged individuals in the Atherosclerosis Risk in Communities (ARIC) study.

RESULTS— The metabolic syndrome was present in ∼23% of individuals without diabetes or prevalent CVD at baseline. Over an average of 11 years of follow-up, 879 incident CHD and 216 ischemic stroke events occurred. Among the components of the metabolic syndrome, elevated blood pressure and low levels of HDL cholesterol exhibited the strongest associations with CHD. Men and women with the metabolic syndrome were ∼1.5 and 2 times more likely to develop CHD than control subjects after adjustment for age, smoking, LDL cholesterol, and race/ARIC center (sex interaction P < 0.03). Similar associations were found between the metabolic syndrome and incident ischemic stroke. Comparison of receiver operating characteristic curves indicated that the metabolic syndrome did not materially improve CHD risk prediction beyond the level achieved by the Framingham Risk Score (FRS).

CONCLUSIONS— Individuals without diabetes or CVD, but with the metabolic syndrome, were at increased risk for long-term cardiovascular outcomes, although statistical models suggested that most of that risk was accounted for by the FRS. Nevertheless, identification of individuals with the metabolic syndrome may provide opportunities to intervene earlier in the development of shared disease pathways that predispose individuals to both CVD and diabetes.
An Evaluation of Candidate Definitions of the Metabolic Syndrome in Adult Asian Indians
Authors: Misra Anoop , Wasir Jasjeet Singh , Pandey Ravinder Mohan
Published: March 2007

OBJECTIVES—We aimed to evaluate eight candidate definitions of the metabolic syndrome (MS) against the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATPIII) definition as the reference for optimally defining MS in adult Asian Indians.

RESEARCH DESIGN AND METHODS—We used clinical and biochemical data from our previous cross-sectional epidemiological studies. Candidate definitions of MS were proposed by modifying the NCEP ATPIII definition. These modifications included the following: waist circumference cutoffs as >90 cm in men and >80 cm in women, BMI cutoff as >23 kg/m2, and a measure of truncal subcutaneous fat (subscapular skinfold thickness [SST] >18 mm).

RESULTS—The highest prevalence (29.9%) of MS was observed by the inclusion of modified cutoffs of waist circumference and BMI and SST in place of the existing cutoffs of waist circumference in the NCEP ATPIII criteria. Further, this modified definition showed the maximum absolute gain in the percentage of prevalence of MS over the NCEP ATPIII definition, and it was the best predictor for MS in subjects with impaired fasting glucose, type 2 diabetes, and different age-groups. The lowest percentage of prevalence of MS was observed with the definition that excluded biochemical variables and blood pressure.

CONCLUSIONS—The criteria for defining MS in adult Asian Indians need revision. Inclusion of modified cutoffs of waist circumference and BMI and measures of truncal subcutaneous fat in the NCEP ATPIII definition requires further validation.
Caffeine Ingestion Is Associated With Reductions in Glucose Uptake Independent of Obesity and Type 2 Diabetes Before and After Exercise Training
Authors: Lee SoJung , Hudson Robert , Kilpatrick Katherine , Graham Terry E. , Ross Robert
Published: March 2007

OBJECTIVE—We investigated the effect of caffeine ingestion on insulin sensitivity in sedentary lean men (n = 8) and obese men with (n = 7) and without (n = 8) type 2 diabetes. We also examined whether chronic exercise influences the relationship between caffeine and insulin sensitivity in these individuals.

RESEARCH DESIGN AND METHODS—Subjects underwent two hyperinsulinemic-euglycemic clamp procedures, caffeine (5 mg/kg body wt) and placebo, in a double-blind, randomized manner before and after a 3-month aerobic exercise program. Body composition was measured by magnetic resonance imaging.

RESULTS—At baseline, caffeine ingestion was associated with a significant reduction (P < 0.05) in insulin sensitivity by a similar magnitude in the lean (33%), obese (33%), and type 2 diabetic (37%) groups in comparison with placebo. After exercise training, caffeine ingestion was still associated with a reduction (P < 0.05) in insulin sensitivity by a similar magnitude in the lean (23%), obese (26%), and type 2 diabetic (36%) groups in comparison with placebo. Exercise was not associated with a significant increase in insulin sensitivity in either the caffeine or placebo trials, independent of group (P > 0.10).

CONCLUSIONS—Caffeine consumption is associated with a substantial reduction in insulin-mediated glucose uptake independent of obesity, type 2 diabetes, and chronic exercise.
Incremental Predictive Value of Carotid Ultrasonography in the Assessment of Coronary Risk in a Cohort of Asymptomatic Type 2 Diabetic Subjects
Authors: Bernard Sophie , Sérusclat André , Targe François , Charrière Sybil , Roth Olivier , Beaune Jacques , Berthezène François , Moulin Philippe
Published: March 2007

OBJECTIVE —Consensus guidelines recommend cardiovascular risk assessment as the initial step of primary prevention. The aim of this study was to evaluate the incremental predictive value for coronary events conferred by carotid ultrasonography in addition to risk assessment by Framingham score and screening for silent myocardial ischemia in a cohort of type 2 diabetic patients.

RESEARCH DESIGN AND METHODS —We prospectively studied 229 patients free of any cardiovascular complication with at least one additional cardiovascular risk factor. At baseline, all patients had an exercise treadmill test, carotid intima-media thickness (IMT) measurement, and coronary risk assessment by Framingham score. Cardiovascular events were registered during a 5-year follow-up period.

RESULTS —Age, carotid IMT, carotid plaques, number of risk factors, Framingham score, and suboptimal exercise electrocardiogram were associated with incident cardiovascular events (P < 0.05). Carotid IMT was an independent predictor of cardiovascular events (P = 0.045). The predictive value for coronary events was similar for carotid IMT and Framingham score as assessed by area under the receiver operating characteristic curves. An improvement in risk prediction was conferred by addition of carotid IMT in a Cox model (global χ2 increased from 14.1 to 18.1, P = 0.035).

CONCLUSIONS —This prospective study confirms that carotid IMT is a marker of cardiovascular risk in this type 2 diabetic cohort, establishes that carotid IMT provides a similar predictive value for coronary events than Framingham score, and suggests that the combination of these two indexes significantly improves risk prediction for these patients.
Glucose Intolerance Is Common in Japanese Patients With Acute Coronary Syndrome Who Were Not Previously Diagnosed With Diabetes
Authors: Hashimoto Koichi , Ikewaki Katsunori , Yagi Hidenori , Nagasawa Hidetaka , Imamoto Satoshi , Shibata Takahiro , Mochizuki Seibu
Published: March 2007

OBJECTIVE—Postprandial hyperglycemia has emerged as a new glycometabolic condition associated with an excessive risk for coronary artery disease. We therefore attempted to evaluate the frequency of postchallenge hyperglycemia in patients with acute coronary syndrome (ACS) who were not previously diagnosed to have diabetes and did not have a fasting glucose concentration of ≥7 mmol/l or an HbA1c level >6.0%. We further correlated the presence of postchallenge hyperglycemia with the extent of coronary atherosclerosis.

RESEARCH DESIGN AND METHODS—In all, 134 consecutive ACS patients who met the above inclusion criteria were studied. An oral glucose tolerance test was performed before discharge.

RESULTS—The mean age, fasting glucose, and HbA1c were 60 years, 5.15 mmol/l, and 5.4%, respectively. Among ACS patients, impaired glucose tolerance (IGT) and diabetes were found in 50 (37%) and 13 patients (10%), respectively. The homeostasis model assessment for insulin resistance did not differ substantially among the normal glucose tolerance (NGT), IGT, and diabetic groups. Insulinogenic index, however, was lower and the number of stenosed vessels higher in diabetic patients compared with NGT patients.

CONCLUSIONS—Postchallenge hyperglycemia, caused primarily by impaired initial insulin secretion, is commonly found in Japanese ACS patients who have not been previously diagnosed with diabetes, and this phenomenon is considered to be associated with advanced coronary atherosclerosis. Therefore, the present study strongly supports the notion that oral glucose tolerance test assessment of postchallenge hyperglycemia is essential to identify any previously undiagnosed diabetes cases among Japanese ACS patients.
Efficient Cutoff Points for Three Screening Tests for Detecting Undiagnosed Diabetes and Pre-Diabetes
Authors: Zhang Ping , Engelgau Michael M. , Valdez Rodolfo , Cadwell Betsy , Benjamin Stephanie M. , Narayan K.M. Venkat
Published: March 2007

OBJECTIVE—Opportunistic screening for undiagnosed type 2 diabetes and pre-diabetes (either impaired glucose tolerance or impaired fasting glucose) is recommended by the American Diabetes Association. The aim of this study was to determine efficient cutoff points for three screening tests for detecting undiagnosed diabetes alone or both undiagnosed diabetes and pre-diabetes.

RESEARCH DESIGN AND METHODS— We estimated the number of individuals with undiagnosed diabetes alone or with both undiagnosed diabetes and pre-diabetes that could be detected by using different cutoff points for each screening test as the product of the prevalence of each condition, the sensitivity of the tests at each cutoff point for identifying each condition, and the number of individuals who would be eligible for screening in the U.S. We estimated the total cost of opportunistic screening by multiplying the cost for screening one person by the number of individuals screened.

RESULTS—The most efficient cutoff points for both detecting pre-diabetes and undiagnosed diabetes (100 mg/dl for the fasting plasma glucose test, 5.0% for the HbA1c test, and 100 mg/dl for the random capillary blood glucose test) were less than those for detecting undiagnosed diabetes alone (110 mg/dl for the fasting plasma glucose test, 5.7% for the HbA1c test, and 120 mg/dl for the random capillary blood glucose test).

CONCLUSIONS—A lower cutoff value should be used when screening for pre-diabetes and undiagnosed diabetes together than when screening for undiagnosed diabetes alone.
Depression and All-Cause and Coronary Heart Disease Mortality Among Adults With and Without Diabetes
Authors: Egede Leonard E. , Nietert Paul J. , Zheng Deyi
Published: March 2007

OBJECTIVE—The aim of this study was to evaluate the effect of depression on all-cause and coronary heart disease (CHD) mortality among adults with and without diabetes.

RESEARCH DESIGN AND METHODS—We studied 10,025 participants in the population-based National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study who were alive and interviewed in 1982 and had complete data for the Center for Epidemiologic Studies Depression Scale. Four groups were created based on diabetes and depression status in 1982: 1) no diabetes, no depression (reference group); 2) no diabetes, depression present; 3) diabetes present, no depression; and i4) diabetes present, depression present. Cox proportional hazards regression models were used to calculate multivariate-adjusted hazard ratios (HRs) of death for each group compared with the reference group.

RESULTS—Over 8 years (83,624 person-years of follow-up), 1,925 deaths were documented, including 522 deaths from CHD. Mortality rate per 1,000 person-years of follow-up was highest in the group with both diabetes and depression. Compared with the reference group, HRs for all-cause mortality were no diabetes, depression present, 1.20 (95% CI 1.03–1.40); diabetes present, no depression 1.88 (1.55–2.27); and diabetes present, depression present, 2.50 (2.04–3.08). HRs for CHD mortality were no diabetes, depression present, 1.29 (0.96–1.74); diabetes present, no depression 2.26 (1.60–3.21); and diabetes present, depression present, 2.43 (1.66–3.56).

CONCLUSIONS—The coexistence of diabetes and depression is associated with a significantly increased risk of death from all causes, beyond that due to having either diabetes or depression alone.
A Prospective Study of Soluble Tumor Necrosis Factor-α Receptor II (sTNF-RII) and Risk of Coronary Heart Disease Among Women With Type 2 Diabetes
Authors: Shai Iris , Schulze Matthias B. , Manson JoAnn E. , Rexrode Kathryn M. , Stampfer Meir J. , Mantzoros Christos , Hu Frank B.
Published: March 2007

OBJECTIVE—Tumor necrosis factor-α (TNF-α), a cytokine secreted by adipose tissue and other cells, might play a role in insulin resistance.

RESEARCH DESIGN AND METHODS—Of 32,826 women from the Nurses’ Health Study who provided blood at baseline, we followed 929 women with type 2 diabetes. During 10 years of follow-up, we documented 124 incident cases of coronary heart disease (CHD).

RESULTS—After adjustment for age, smoking, BMI, and other cardiovascular risk factors, the relative risks (RRs) comparing extreme quartiles of soluble TNF-α receptor II (sTNF-RII) were 2.48 (95% CI 1.08–5.69; P = 0.034) for myocardial infarction (MI) and 2.02 (1.17–3.48; P = 0.003) for total CHD. The probability of developing CHD over 10 years was higher among diabetic subjects with substantially higher levels of both sTNF-RII (>75th percentile) and HbA1c (>7%), compared with diabetic subjects with lower levels (25% vs. 7%, P < 0.0001). Diabetic subjects with only higher sTNF-RII or HbA1c had similar (16–17%) risk. In a multivariate model, diabetic subjects with higher levels of both sTNF-RII and HbA1c had an RR of 3.66 (1.85–7.22) for MI and 3.03 (1.82–5.05) for total CHD, compared with those with lower levels of both biomarkers.

CONCLUSIONS—Increased levels of sTNF-RII were strongly associated with risk of CHD among diabetic women, independent of hyperglycemia.
Bimodality of 2-h Plasma Glucose Distributions in Whites
Authors: Fan Juanjuan , May Susanne J. , Zhou Yue , Barrett-Connor Elizabeth
Published: March 2007

OBJECTIVE—Several studies have shown a bimodal curve in the distribution of glucose in populations with a high prevalence of type 2 diabetes, but bimodality has not been reported among whites of Northern European ancestry. It is not clear whether this difference reflects the lower prevalence of diabetes, obscuring a second mode, or implies a more fundamental difference between whites and nonwhites. We investigate this issue by studying glucose distributions in older white patients.

RESEARCH DESIGN AND METHODS—A study of diabetes was conducted among older community-dwelling white residents of a suburban Southern California community between 1984 and 1987. Two-hour plasma glucose data were collected from 2,326 older white men and women aged 23–92. To investigate bimodality of glucose distributions, we fit unimodal and bimodal normal models to 2-h plasma glucose concentrations transformed by the Box-Cox family of transformations.

RESULTS—We found that the bimodal normal mixture model fit the data significantly better than the unimodal skewed distribution model for both sexes and all age-groups except those ≥80 years. The cut points separating the two modes were generally within the 11.1- to 13.6-mmol/l range.

CONCLUSIONS—The bimodality of glucose distributions among whites, combined with previous findings, indicates that this phenomenon may be universal. A smaller second mode in our study compared with other studies suggests that whites have diabetes susceptibility but may require more obesity to demonstrate it. With increasing obesity in the U.S., the predicted epidemic of diabetes may affect all ethnic groups including whites.
Use of Multisystemic Therapy to Improve Regimen Adherence Among Adolescents With Type 1 Diabetes in Chronic Poor Metabolic Control
Authors: Ellis Deborah A. , Frey Maureen A. , Naar-King Sylvie , Templin Thomas , Cunningham Phillippe , Cakan Nedim
Published: March 2007

OBJECTIVE—The aim of this study was to determine whether multisystemic therapy (MST), an intensive, home-based psychotherapy, could improve adherence and metabolic control and decrease rates of hospital utilization among adolescents with chronically poorly controlled type 1 diabetes.

RESEARCH DESIGN AND METHODS—A randomized controlled trial was conducted with 127 adolescents with type 1 diabetes and chronically poor metabolic control (HbA1c [A1C] ≥8% for the past year) who received their diabetes care in a children’s hospital located in a major Midwestern city. Participants randomly assigned to MST received treatment for ∼6 months. Data were collected at baseline and at 7 months posttest (i.e., treatment termination). Changes in A1C adherence, as measured by semistructured interviews and blood glucose meters and hospital admissions and emergency department visits, were assessed.

RESULTS—In intent-to-treat analyses, participation in MST was associated with significant improvements in the frequency of blood glucose testing as assessed by blood glucose meter readings (F[1,125] = 16.75, P = 0.001) and 24-h recall interviews (F[1,125] = 6.70, P = 0.011). Participants in MST also had a decreasing number of inpatient admissions, whereas the number of inpatient admissions increased for control subjects (F[1,125] = 6.25, P = 0.014). Per protocol analyses replicated intent-to-treat analyses but also showed a significant improvement in metabolic control for adolescents receiving MST compared with control subjects (F[1,114] = 4.03, P = 0.047).

CONCLUSIONS—Intensive, home-based psychotherapy improves the frequency of blood glucose testing and metabolic control and decreases inpatient admissions among adolescents with chronically poorly controlled type 1 diabetes.