bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic Value of Dobutamine Stress Echocardiography in Patients With Diabetes
Authors: Sozzi Fabiola B. , Elhendy Abdou , Roelandt Jos R.T.C. , van Domburg Ron T. , Schinkel Arend F.L. , Vourvouri Eleni C. , Bax Jeroen J. , De Sutter Johan , Borghetti Alberico , Poldermans Don
Published: March 2007

OBJECTIVE—The aim of this study was to assess the incremental value of dobutamine stress echocardiography (DSE) for the risk stratification of diabetic patients who are unable to perform an adequate exercise stress test. Exercise capacity is frequently impaired in patients with diabetes. The role of pharmacologic stress echocardiography in the risk stratification of diabetic patients has not been well defined.

RESEARCH DESIGN AND METHODS—We studied 396 diabetic patients (mean age 61 ± 11 years, 252 men [64%]) with limited exercise capacity who underwent DSE for evaluation of known or suspected coronary artery disease (CAD). End points were hard cardiac events (cardiac death and nonfatal myocardial infarction) and all causes of mortality.

RESULTS—During a median follow-up of 3 years, 97 patients (24%) died (55 cardiac deaths), and 27 patients had nonfatal myocardial infarction. In an incremental multivariate analysis model, clinical predictors of hard cardiac events were history of congestive heart failure, previous myocardial infarction, hypercholesterolemia, and ejection fraction at rest. The percentage of ischemic segments was incremental to the clinical model in the prediction of hard cardiac events (χ2 = 37 vs. 18, P < 0.05). Clinical predictors of all causes of mortality were history of congestive heart failure, age, hypercholesterolemia, and ejection fraction at rest. Wall motion score index at peak stress was incremental to the clinical model in the prediction of mortality (χ2 = 52 vs. 43, P < 0.05).

CONCLUSIONS—DSE provides incremental data for the prediction of mortality and hard cardiac events in patients with diabetes who are unable to perform an adequate exercise stress test.
High Incidence of Tacrolimus-Associated Posttransplantation Diabetes in the Korean Renal Allograft Recipients According to American Diabetes Association Criteria
Authors: Cho Young Min , Park Kyong Soo , Jung Hye Seung , Jeon Hyun Jung , Ahn Curie , Ha Jongwon , Kim Sang Joon , Rhee Byoung Doo , Kim Seong Yeon , Lee Hong Kyu
Published: March 2007

OBJECTIVE—The incidence of posttransplantation diabetes mellitus (PTDM) has been reported to vary according to different study populations or different definitions. In this study, using American Diabetes Association criteria, the incidence and clinical characteristics of PTDM in Korean renal allograft recipients undergoing tacrolimus-based immunosuppression were examined.

RESEARCH DESIGN AND METHODS—A total of 21 patients taking tacrolimus as primary immunosuppressant were recruited and tested with a serial 75-g oral glucose tolerance test at 0, 1, 3, and 6 months after renal transplantation.

RESULTS—The cumulative incidence of PTDM was 52.4% at 1 month and 57.1% at 3 and 6 months. The baseline characteristics of the PTDM group were old age (especially >40 years), a high BMI, a high fasting glucose level, a high plasma insulin level, and increased insulin resistance. Among these parameters, old age was the only independent risk factor. The insulin secretory capacity in the PTDM group was maximally suppressed 3 months after transplantation. Thereafter, it was gradually restored along with dose reduction of tacrolimus.

CONCLUSIONS—Routine screening for PTDM is necessary in patients over 40 years of age who are undergoing a relatively higher dose tacrolimus therapy during the early course of postrenal transplantation.
Oral Magnesium Supplementation Improves Insulin Sensitivity and Metabolic Control in Type 2 Diabetic Subjects
Authors: Rodríguez-Morán Martha , Guerrero-Romero Fernando
Published: March 2007

OBJECTIVE—To determine whether oral magnesium supplementation (as magnesium chloride [MgCl2] solution) improves both insulin sensitivity and metabolic control in type 2 diabetic subjects with decreased serum magnesium levels.

RESEARCH DESIGN AND METHODS—This study was a clinical randomized double-blind placebo-controlled trial. A total of 63 subjects with type 2 diabetes and decreased serum magnesium (serum magnesium levels ≤0.74 mmol/l) treated by glibenclamide received either 50 ml MgCl2 solution (containing 50 g MgCl2 per 1,000 ml solution) or placebo daily for 16 weeks. Chronic diarrhea, alcoholism, use of diuretic and/or calcium antagonist drugs, and reduced renal function were exclusion criteria. Homeostasis model assessment for insulin resistance (HOMA-IR) was used as the parameter of insulin sensitivity and glucose and HbA1c as parameters of metabolic control.

RESULTS—At the end of the study, subjects who received magnesium supplementation showed significant higher serum magnesium concentration (0.74 ± 0.10 vs. 0.65 ± 0.07 mmol/l, P = 0.02) and lower HOMA-IR index (3.8 ± 1.1 vs. 5.0 ± 1.3, P = 0.005), fasting glucose levels (8.0 ± 2.4 vs. 10.3 ± 2.1 mmol/l, P = 0.01), and HbA1c (8.0 ± 2.4 vs. 10.1 ± 3.3%, P = 0.04) than control subjects.

CONCLUSIONS—Oral supplementation with MgCl2 solution restores serum magnesium levels, improving insulin sensitivity and metabolic control in type 2 diabetic patients with decreased serum magnesium levels.
Progression of Retinopathy During Pregnancy in Type 1 Diabetic Women Treated With Insulin Lispro
Authors: Loukovaara Sirpa , Immonen Ilkka , Teramo Kari Atle , Kaaja Risto
Published: March 2007

OBJECTIVE— To evaluate the progression of retinopathy during pregnancy and postpartum in (insulin-dependent) women with type 1 diabetes treated with insulin lispro or with regular human insulin.

RESEARCH DESIGN AND METHODS— A prospective open study of 69 pregnant women with diabetes was performed. A total of 36 of the women were treated with insulin lispro (lispro group) and 33 were treated with conventional short-acting human insulin (regular insulin group). The retinopathy level was estimated by color fundus photography every trimester and postpartum. Glycemic control during pregnancy, hypoglycemia (blood glucose level <3 mmol/l) in 24-h glucose profile, blood pressure, and proteinuria were registered.

RESULTS— HbA1c values were similar at baseline in the first trimester but thereafter were lower in the lispro group than in the regular insulin group throughout pregnancy (P = 0.022, repeated-measures ANOVA). The number of hypoglycemic episodes did not differ between the treatment groups. In multivariable logistic regression analysis with retinopathy severity (Diabetes Control and Complications Trial level) in the third trimester as the dependent variable, only nulliparity qualified as a predictor in the model [Exp(B) = 4.0, 95% CI 1.1–13.7, P = 0.030]. Factors such as duration of diabetes, type of insulin used, mean HbA1c level throughout pregnancy, blood pressure (systolic or diastolic), preeclampsia in the current pregnancy, smoking, or prepregnancy planning did not explain the retinopathy progression.

CONCLUSIONS— Insulin lispro improves glycemic control during diabetic pregnancy compared with regular insulin with no adverse impact on progression of diabetic retinopathy.
Factors Responsible for Development From Normal Glucose Tolerance to Isolated Postchallenge Hyperglycemia
Authors: Suzuki Haruhiko , Fukushima Mitsuo , Usami Masaru , Ikeda Masaki , Taniguchi Ataru , Nakai Yosikatsu , Matsuura Toshifumi , Kuroe Akira , Yasuda Koichiro , Kurose Takeshi , Seino Yutaka , Yamada Yuichiro
Published: March 2007

OBJECTIVE—Isolated postchallenge hyperglycemia (IPH), defined as fasting plasma glucose (FPG) level <7.0 mmol/l and 2-h plasma glucose (PG) level ≥11.1 mmol/l, is a subtype of early-stage diabetes. This study evaluates the metabolic profiles of insulin secretion and insulin sensitivity in IPH to clarify the factors responsible for development of this form of type 2 diabetes.

RESEARCH DESIGN AND METHODS—We conducted cross-sectional analysis of 231 Japanese men aged 20–70 years. The subjects were classified into the following three groups, based on the results of a 75-g oral glucose tolerance test (OGTT): 1) normal glucose tolerance (NGT), defined as FPG level <6.1 mmol/l and 2-h PG level <7.8 mmol/l (n = 89); 2) impaired glucose tolerance (IGT), defined as FPG level <7.0 mmol/l and 2-h PG level of 7.8–11.1 mmol/l (n = 94); and 3) IPH (n = 48). We compared the three groups for insulin secretion (insulinogenic index) and insulin sensitivity (index of insulin resistance using homeostasis model assessment [HOMA-IR]).

RESULTS—The insulinogenic index in IPH was the lowest of the three groups (P < 0.001 versus NGT). The HOMA-IR in the IGT and IPH groups were significantly higher than in the NGT group (P < 0.001), but both were similar. By linear regression analysis, the insulinogenic index rather than fasting insulin or HOMA-IR was the more significant factor in the 2-h PG level in IGT and IPH.

CONCLUSIONS—Subjects with IPH exhibited distinctly impaired early-phase insulin secretion and only mild insulin resistance, indicating that reduced insulin secretion is the primary determinant of deterioration from NGT to IGT and IPH in development of type 2 diabetes in these subjects.
Common Cholesteryl Ester Transfer Protein Gene Polymorphisms and the Effect of Atorvastatin Therapy in Type 2 Diabetes
Authors: van Venrooij Francine V. , Stolk Ronald P. , Banga Jan-Dirk , Sijmonsma Tjeerd P. , van Tol Arie , Erkelens D. Willem , Dallinga-Thie Geesje M. ,   for the DALI study group
Published: March 2007

OBJECTIVE—The cholesteryl ester transfer protein (CETP) plays a key role in the remodeling of triglyceride (TG)-rich and HDL particles. Sequence variations in the CETP gene may interfere with the effect of lipid-lowering treatment in type 2 diabetes.

RESEARCH DESIGN AND METHODS—We performed a 30-week randomized double-blind placebo-controlled trial with atorvastatin 10 mg (A10) and 80 mg (A80) in 217 unrelated patients with diabetes.

RESULTS—CETP TaqIB and A-629C polymorphisms were tightly concordant (P < 0.001). At baseline, B1B1 carriers had lower plasma HDL cholesterol (0.99 ± 0.2 vs. 1.11 ± 0.2 mmol/l, P < 0.05), higher CETP mass (2.62 ± 0.8 vs. 2.05 ± 0.4 mg/l, P < 0.001), and slightly increased, though not significant, plasma TGs (2.7 ± 1.05 vs. 2.47 ± 0.86, P = 0.34) compared with B2B2 carriers. Atorvastatin treatment significantly reduced CETP mass dose-dependently by 18% (A10) and 29% (A80; both vs. placebo P < 0.001, A10-A80 P < 0.001). CETP mass and activity were strongly correlated (r = 0.854, P < 0.0001). CETP TaqIB polymorphism appeared to modify the effect of atorvastatin on HDL cholesterol elevation (B1B1 7.2%, B1B2 6.1%, B2B2 0.5%; P < 0.05), TG reduction (B1B1 39.7%, B1B2 38.4%, B2B2 18.4%; P = 0.08), and CETP mass reduction (B1B1 32.1%, B1B2 29.6%, B2B2 21.9%; P = 0.27, NS). Similar results were obtained for the A-629C polymorphism.

CONCLUSIONS—In conclusion, the B1B1/CC carriers of the CETP polymorphisms have a more atherogenic lipid profile, including low HDL, and they respond better to statin therapy. These results favor the hypothesis that CETP polymorphisms modify the effect of statin treatment and may help to identify patients who will benefit most from statin therapy.
The National Diabetes Register in Sweden
Authors: Gudbjörnsdottir Soffia , Cederholm Jan , Nilsson Peter M. , Eliasson Björn ,   for the Steering Committee of the Swedish National Diabetes Register
Published: March 2007

OBJECTIVE—To monitor glycemic control, treatable risk factors, and treatment profile for quality assessment of diabetes care on a national scale.

RESEARCH DESIGN AND METHODS—Four samples of 23,546, 32,903, 30,311, and 29,769 patients with diabetes (1996–1999) were studied based on a repeated national screening and quality assessment of diabetes care by the National Diabetes Register, Sweden, with participation of both hospitals and primary health care. Clinical characteristics included were age, sex, diabetes duration and treatment, glycemic control (HbA1c), office blood pressure (BP), BMI, smoking habits, and use of lipid-lowering drugs in patients with type 1 or type 2 diabetes.

RESULTS—Favorable decreases of mean HbA1c and BP values were registered during the 4-year study period for both type 1 (HbA1c 7.5–7.3% and BP 130/75–130/74 mmHg) and type 2 diabetic patients (HbA1c 7.0–6.7% and BP 151/82–147/80 mmHg). Treatment aims of HbA1c and BP levels were also achieved in increasing proportions for type 1 (HbA1c <7.5%: 50–58% and BP ≤140/85 mmHg: 77–79%), and type 2 diabetic patients (HbA1c <7.5%: 66–73% and BP ≤140/85 mmHg: 32–42%). The use of lipid-lowering drugs increased for type 1 (4–11%) and type 2 diabetic patients (10–22%). In type 2 diabetic patients, treatment with oral agents alone decreased, but combination therapy (insulin and oral agents) increased during the study period. Mean BMI increased during 1996–1999 in type 2 diabetic patients. High HbA1c and BP values in 1999 were predicted by high BMI values 1996 and by high increase of BMI during the period, independent of diabetes duration, age, and sex.

CONCLUSIONS—Decreasing mean HbA1c and BP levels and the wider use of lipid-lowering drugs during the late 1990s in patients with diabetes in a national sample from Sweden should translate into clinical benefits regarding micro- and macrovascular complications as well as diabetes-related mortality.
Systematic Review of Herbs and Dietary Supplements for Glycemic Control in Diabetes
Authors: Yeh Gloria Y. , Eisenberg David M. , Kaptchuk Ted J. , Phillips Russell S.
Published: March 2007

OBJECTIVE—To conduct a systematic review of the published literature on the efficacy and safety of herbal therapies and vitamin/mineral supplements for glucose control in patients with diabetes.

RESEARCH DESIGN AND METHODS—We conducted an electronic literature search of MEDLINE, OLDMEDLINE, Cochrane Library Database, and HealthSTAR, from database inception to May 2002, in addition to performing hand searches and consulting with experts in the field. Available clinical studies published in the English language that used human participants and examined glycemic control were included. Data were extracted in a standardized manner, and two independent investigators assessed methodological quality of randomized controlled trials using the Jadad scale.

RESULTS—A total of 108 trials examining 36 herbs (single or in combination) and 9 vitamin/mineral supplements, involving 4,565 patients with diabetes or impaired glucose tolerance, met the inclusion criteria and were analyzed. There were 58 controlled clinical trials involving individuals with diabetes or impaired glucose tolerance (42 randomized and 16 nonrandomized trials). Most studies involved patients with type 2 diabetes. Heterogeneity and the small number of studies per supplement precluded formal meta-analyses. Of these 58 trials, the direction of the evidence for improved glucose control was positive in 76% (44 of 58). Very few adverse effects were reported.

CONCLUSIONS—There is still insufficient evidence to draw definitive conclusions about the efficacy of individual herbs and supplements for diabetes; however, they appear to be generally safe. The available data suggest that several supplements may warrant further study. The best evidence for efficacy from adequately designed randomized controlled trials (RCTs) is available for Coccinia indica and American ginseng. Chromium has been the most widely studied supplement. Other supplements with positive preliminary results include Gymnema sylvestre, Aloe vera, vanadium, Momordica charantia, and nopal.
Processes and Outcomes of Care for Diabetic Acute Myocardial Infarction Patients in Ontario
Authors: Alter David A. , Khaykin Yaariv , Austin Peter C. , Tu Jack V. , Hux Janet E.
Published: March 2007

OBJECTIVE—To compare the health service utilization and long-term outcomes of acute myocardial infarction (AMI) patients with and without diabetes in Ontario.

RESEARCH DESIGN AND METHODS—We examined 25,697 patients from Ontario (6,052 and 19,645 patients with and without diabetes, respectively) who were hospitalized because of AMI between 1 April 1992 and 31 December 1993. Using linked administrative databases, we determined the use of invasive cardiac procedures at 1 year as well as the intensity of specialty follow-up care and use of evidence-based pharmacotherapies (among elderly individuals) within the first 90 days of hospital discharge. Outcomes examined included mortality and recurrent cardiac admissions at 30 days and 5 years post AMI. Multivariable analyses adjusted for sociodemographic and case-mix characteristics, attending physician specialty, and admitting hospital characteristics.

RESULTS—Despite being at significantly higher risk for death at baseline, diabetic patients were less likely to be followed-up by a cardiologist (22.2 vs. 25.6%, P < 0.001), to receive myocardial revascularization (12.6 vs. 14.9%, P < 0.001), to receive β-blockers (34.2 vs. 44.0%, P < 0.001), and to receive aspirin therapy (59.7 vs. 63.5%, P < 0.001) after AMI than their nondiabetic counterparts. Diabetes was an important independent predictor of 5-year morbidity (adjusted hazard ratio 1.52, 95% CI 1.45–1.59) and 5-year mortality outcomes (1.57, 1.50–1.63). Variations in processes of care were marginally associated with higher nonfatal complication rates for diabetic patients.

CONCLUSIONS—When managing AMI patients with diabetes in Ontario, physician treatment aggressiveness does not correspond appropriately to the baseline risk of patients.
Fibrinogen Is a Marker for Nephropathy and Peripheral Vascular Disease in Type 1 Diabetes
Authors: Klein Richard L. , Hunter Steven J. , Jenkins Alicia J. , Zheng Deyi , Semler Andrea J. , Clore Jennifer , Garvey W. Timothy ,   The DCCT/EDIC Study Group
Published: March 2007

ABSTRACT— We examined whether plasma fibrinogen levels and the β-fibrinogen gene G−455→A polymorphism were related to microvascular or macrovascular disease in patients (n = 909) with type 1 diabetes enrolled in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/ EDIC). Univariate regression showed that fibrinogen levels were correlated with BMI (r = 0.15; P < 0.0001), HbA1c (r = 0.11; P = 0.0014), total cholesterol (r = 0.17; P < 0.0001), and LDL cholesterol (r = 0.16; P < 0.0001) in all patients. In men, but not women, waist-to-hip ratio (r = 0.20; P < 0.0001) and triglycerides (r = 0.13; P = 0.0047) also became powerful predictors of fibrinogen level; in women, but not men, fibrinogen was correlated with both diastolic (r = 0.16; P = 0.0011) and systolic (r = 0.11; P = 0.0241) blood pressure. Fibrinogen was correlated with urinary albumin excretion rates in men (r = 0.13; P = 0.0033), but not in women. In both sexes, however, the development of proteinuria (albumin excretion >300 mg/24 h) was accompanied by 1.5-fold increment in plasma fibrinogen compared with patients with normal excretion or microalbuminuria. In addition, high fibrinogen levels were associated with a lower average ankle-brachial index in women (r = −0.13; P = 0.0075), but not men. Multiple regression analyses demonstrated that plasma fibrinogen was independently correlated with high albumin excretion rate in men, and with low average ankle-brachial index in women. Fibrinogen was not correlated with the severity of retinopathy. Carotid artery intima-medial thickness was not correlated with fibrinogen, and the G−455→A polymorphism in the 5′ promoter region of the β-fibrinogen gene did not influence circulating fibrinogen levels. However, the presence of the more common G−455 allele was associated with greater intima-medial thickness in the internal carotid artery (ANCOVA P = 0.045). Last, hyperfibrinogenemia in type 1 diabetes is associated with components of the insulin resistance syndrome trait cluster, and the association is influenced by sex.
Association of Hypoglycemia and Cardiac Ischemia
Authors: Desouza Cyrus , Salazar Holger , Cheong Benjamin , Murgo Joseph , Fonseca Vivian
Published: March 2007

OBJECTIVE—In some studies intensive diabetes treatment in patients with type 2 diabetes may be associated with increased cardiovascular events. It is not clear whether these events are related to hypoglycemic episodes. To determine whether episodes of hypoglycemia were more likely to be associated with cardiac ischemia than normoglycemia or hyperglycemia, we carried out a study in 21 patients with coronary artery disease (CAD) and type 2 diabetes treated with insulin who had good glycemic control.

RESEARCH DESIGN AND METHODS—We carried out 72-h continuous glucose monitoring along with simultaneous cardiac Holter monitoring for ischemia. Patients also recorded symptoms of cardiac ischemia (chest pain) and symptoms of hypoglycemia.

RESULTS—Satisfactory continuous glucose monitoring system recordings were obtained in 19 patients. We recorded 54 episodes of hypoglycemia (blood glucose <70 mg/dl; 26 of these were symptomatic) and 59 episodes of hyperglycemia (blood glucose >200 mg/dl; none symptomatic). Of the 54 episodes of hypoglycemia, 10 were associated with symptoms of chest pain, during 4 of which electrocardiographic abnormalities were documented. In contrast, only 1 episode of chest pain occurred during 59 episodes of hyperglycemia. No chest pain or electrocardiographic abnormalities occurred when the blood glucose was within the normal range. The difference between the frequency of ischemia during hypoglycemia and the frequency during both hyperglycemia and normoglycemia was statistically significant (P < 0.01). There were 50 episodes during which the blood glucose changed by >100 mg over a 60-min period, and ischemic symptoms occurred during 9 of these episodes (P < 0.01 compared with stable normoglycemia or hyperglycemia).

CONCLUSIONS—Hypoglycemia is more likely to be associated with cardiac ischemia and symptoms than normoglycemia and hyperglycemia, and it is particularly common in patients who experience considerable swings in blood glucose. These data may be important in the institution of insulin treatment and attempting near-normal glycemia in patients with known CAD. Further research is needed to determine strategies to prevent ischemia associated with hypoglycemia.
Long-Term Renoprotective Effects of Losartan in Diabetic Nephropathy
Authors: Andersen Steen , Tarnow Lise , Cambien Francois , Rossing Peter , Juhl Tina R. , Deinum Jaap , Parving Hans-Henrik
Published: March 2007

OBJECTIVE—Several observational follow-up studies have found that the D allele of the insertion (I)/deletion (D) polymorphism of the ACE gene (ACE/ID) is associated with an increased risk of renal function loss, even during ACE inhibition. Therefore, we investigated the long-term effect of the angiotensin II subtype-1 (AT1) receptor antagonist losartan (100 mg o.d.) on kidney function in II and DD type 1 diabetic patients with diabetic nephropathy.

RESEARCH DESIGN AND METHODS—A total of 54 hypertensive type 1 diabetic patients with diabetic nephropathy homozygous for the insertion (n = 26) or the deletion (n = 28) allele were included in the study. After a 4-week washout, the patients received losartan (tablet, 100 mg o.d.) and were followed prospectively with a mean follow-up period of 36 months. Patients and investigators were blinded to ACE genotypes. At baseline, after 2 and 4 months and every 6 months thereafter, glomerular filtration rate (GFR), albuminuria, and 24-h blood pressure were determined.

RESULTS—At baseline, GFR, albuminuria, and blood pressure were similar in the two genotype groups, II versus DD: mean (SD), 86 (22) vs. 88 (24) ml · min–1 · 1.73 m–2; median (interquartile range), 1,134 (598–2,023) vs. 1,451 (893–1,766) mg/24 h; and mean (SD), 156/82 (17/9) vs. 153/80 (17/11) mmHg, respectively. GFR decreased similarly in both genotype groups, versus DD, respectively (P = 0.4): geometric mean (95% CI), 2.9 (2.0–4.2) vs. 3.4 (2.3–5.1) ml · min–1 · year–1. Albuminuria and arterial blood pressure were significantly reduced during the study; no differences were noted between groups. During follow-up, albuminuria was decreased by 75% (95% CI 59–85) and 73% (56–83) in the II and DD groups, respectively (P < 0.01 vs. baseline). Mean systolic and diastolic blood pressures were 139/74 mmHg (14/8) in both genotype groups during the study (P < 0.01 vs. baseline).

CONCLUSIONS—In contrast to previous observational studies with ACE inhibitors, long-term treatment with losartan has similar beneficial renoprotective effects on progression of diabetic nephropathy in hypertensive type 1 diabetic patients with ACE II and DD genotypes.
Insulin Resistance and Cardiovascular Events With Low HDL Cholesterol
Authors: Robins Sander J. , Rubins Hanna Bloomfield , Faas Fred H. , Schaefer Ernst J. , Elam Marshall B. , Anderson James W. , Collins Dorothea ,   on behalf of the VA-HIT Study Group
Published: March 2007

OBJECTIVE—To assess the effect of insulin resistance and the benefit of the fibrate, gemfibrozil, on the incidence of major cardiovascular events in subjects with low HDL cholesterol and a broad range of triglyceride values who participated in the Veterans Affairs High Density Lipoprotein Intervention Trial (VA-HIT).

RESEARCH DESIGN AND METHODS—This intention-to-treat analysis, specified as a secondary objective in VA-HIT, determined using Cox proportional hazards models the 5-year combined incidence of nonfatal myocardial infarction, coronary heart disease (CHD) death, or stroke in relation to the presence or absence of insulin resistance (defined by the highest tertile of the homeostasis model assessment of insulin resistance, HOMA-IR) in conjunction with lower and higher levels of HDL cholesterol and triglycerides. The study population consisted of 2,283 men with known coronary heart disease (CHD), treated with either placebo or gemfibrozil, who could be subdivided into groups with diabetes with or without insulin resistance, with no diabetes but insulin resistance, and with neither diabetes nor insulin resistance.

RESULTS—With insulin resistance there was a significantly higher relative risk (RR) of a cardiovascular event both with diabetes (RR of 1.62 with 95% CI of 1.28–2.06) and without diabetes (RR of 1.43 with 95% CI of 1.03–1.98) than without insulin resistance. Throughout both lower and higher ranges of HDL cholesterol and triglycerides, the rate of new cardiovascular events and the reduction of events with gemfibrozil was greater in subjects with insulin resistance than without, despite the finding that an increase in HDL cholesterol and a decrease in triglycerides with gemfibrozil was less with insulin resistance than without insulin resistance.

CONCLUSIONS—Results show that in VA-HIT the occurrence of a new cardiovascular event and the benefit of fibrate therapy was much less dependent on levels of HDL cholesterol or triglycerides than on the presence or absence of insulin resistance.
A Model to Determine Workforce Needs for Endocrinologists in the United States Until 2020
Authors: Rizza Robert A. , Vigersky Robert A. , Rodbard Helena W. , Ladenson Paul W. , Young William F. , Surks Martin I. , Kahn Richard , Hogan Paul F.
Published: March 2007

The objective of this study was to define the workforce needs for the specialty of Endocrinology, Diabetes, and Metabolism in the United States between 1999 and 2020. An interactive model of factors likely to influence the balance between the supply and demand of endocrinologists during the next 20 years was constructed. The model used data from a wide range of sources and was developed under the guidance of a panel of experts derived from sponsoring organizations of endocrinologists. We determined current and projected numbers and demographics of endocrinologists in the U.S. workforce and the anticipated balance between supply and demand from 1999 to 2020. There were 3,623 adult endocrinologists in the workforce in 1999, of which 2,389 (66%) were in office-based practice. Their median age was 49 years. Both total office visits and services performed by endocrinologists (particularly for diabetes) increased substantially during the 1990s. Waiting time for an initial appointment is presently longer for endocrinologists than for other physicians. Compared with a balanced, largely closed-staff health maintenance organization, the current national supply of endocrinologists is estimated to be 12% lower than demand. The number of endocrinologists entering the market has continuously fallen over the previous 5 years, from 200 in 1995 to 171 in 1999. Even if this downward trend were abruptly stopped, the model predicts that demand will exceed supply from now until 2020. While this gap narrows from 2000 to 2008 due to projected growth of managed care, it widens thereafter due to the aging of both the population and the endocrine workforce. Inclusion of other factors such as projected real income growth and increased prevalence of age-related endocrine disorders (e.g., diabetes and osteoporosis) further accentuates the deficit. If the number of endocrinologists entering the workforce remains at 1999 levels, demand will continue to exceed supply from now through 2020 for adult endocrinologists, and the gap will widen progressively from 2010 onward. The present analysis indicates that the number of endocrinologists entering the workforce will not be sufficient to meet future demand. These data suggest that steps should be taken to stop the ongoing decline in the number of endocrinologists in training and consideration should be given to actions designed to increase the number of endocrinologists in practice in the years ahead.
Developing a Screening Program to Detect Sight-Threatening Diabetic Retinopathy in South India
Authors: Namperumalsamy Perumalsamy , Nirmalan Praveen K. , Ramasamy Kim
Published: March 2007

OBJECTIVE—To develop a screening protocol for detection of sight-threatening diabetic retinopathy in south India.

RESEARCH DESIGN AND METHODS—We performed ophthalmic examinations, including posterior segment examination, using indirect ophthalmoscopy to detect sight-threatening retinopathy in patients with diabetes in screening camps targeting a high-risk population.

RESULTS—We examined 3,949 persons with diabetes in 32 screening camps over a 13-month period beginning July 2001. Most of the patients (93.6%) were aware of their diabetic status, and 84.2% of those aware of their diabetes status were on treatment. One-fifth of those screened had evidence for any retinopathy; only 6.1% of these persons had evidence of past ophthalmic treatment for retinopathy. Only one-quarter of those diagnosed with worse than mild retinopathy came for follow-up to the base hospital within 2 months.

CONCLUSIONS—Screening high-risk groups for sight-threatening retinopathy using indirect ophthalmoscopy may be a useful short-term alternative for India until retinal photography becomes affordable. In addition to strategies to improve coverage, strategies for better follow-up of subjects screened also need to be evolved.
l-Arginine-Induced Vasodilation of the Renal Vasculature Is Not Altered in Hypertensive Patients With Type 2 Diabetes
Authors: Delles Christian , Schneider Markus P. , Oehmer Sebastian , Fleischmann Erwin H. , Schmieder Roland E.
Published: March 2007

OBJECTIVE—Diabetes, arterial hypertension, hypercholesterolemia, and aging are associated with endothelial dysfunction in various vasculatures. Endothelium-dependent vasodilation of the renal vasculature cannot be easily assessed, but infusion of l-arginine, the substrate of endothelial nitric oxide synthase, leads to an increase in renal plasma flow (RPF) in humans. We have examined the effect of l-arginine infusion on renal hemodynamics in hypertensive patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS—Twenty-three elderly patients with type 2 diabetes (age, 65 ± 6 years; HbA1c, 7.8 ± 1.6%) with coexisting arterial hypertension (158 ± 19/83 ± 11 mmHg) and elevated cholesterol levels (total cholesterol, 215 ± 33 mg/dl) were examined. These patients were compared with a young and healthy reference group (n = 20; age, 26 ± 2 years). The effect of l-arginine infusion (100 mg/kg over 30 min) on RPF and glomerular filtration rate were measured using the constant input clearance technique with p-aminohippurate and inulin, respectively.

RESULTS—l-Arginine infusion similarly influenced renal hemodynamics in patients and reference subjects: RPF increased by 7 ± 11 and 7 ± 11% in diabetic and reference subjects, respectively (P = NS). Other parameters of renal hemodynamics such as glomerular filtration rate (5 ± 5 vs. 4 ± 4%) and filtration fraction (−1 ± 8 vs. −1 ± 9%) were not significantly different between diabetic and reference subjects, too.

CONCLUSIONS—l-Arginine-induced vasodilation of the renal vasculature is not different between a group of hypertensive diabetic patients and a young, healthy reference group. These data were obtained using low-dose l-arginine infusion.
Human Epidermal Growth Factor Enhances Healing of Diabetic Foot Ulcers
Authors: Tsang Man Wo , Wong Wan Keung R. , Hung Chi Sang , Lai Kwok-Man , Tang Wegin , Cheung Elaine Y.N. , Kam Grace , Leung Leo , Chan Chi Wai , Chu Chung Min , Lam Edward K.H.
Published: March 2007

OBJECTIVE—To study the healing effect of recombinant human epidermal growth factor (hEGF) on diabetic foot ulcers.

RESEARCH DESIGN AND METHODS—A total of 127 consecutive patients were screened and 61 diabetic subjects were recruited into this double-blind randomized controlled study. Predetermined criteria were used for diagnosis and classification of the diabetic wound. The patients were randomized into three groups. All patients attended our Diabetes Ambulatory Care Center every other week for joint consultation with the diabetologist and the podiatrist. Group 1 (control) was treated with Actovegin 5% cream (Actovegin), group 2 with Actovegin plus 0.02% (wt/wt) hEGF, and group 3 with Actovegin plus 0.04% (wt/wt) hEGF. The study end point was the complete closure of the wound. Failure to heal was arbitrarily defined as incomplete healing after 12 weeks.

RESULTS—Final data were obtained from 61 patients randomly assigned into three groups. The mean ages of the patients, wound sizes, wound duration, metabolic measurements, and comorbidities were comparable within groups, except that group 3 had more female patients. Mean follow-up for the patients was 24 weeks. Data were cutoff at 12 weeks, and results were analyzed by intention to treat. After 12 weeks, in group 1 (control) eight patients had complete healing, two patients underwent toe amputation, and nine had nonhealing ulcers. In group 2 (0.02% [wt/wt] hEGF) 12 patients experienced wound healing, 2 had toe amputations, and 7 had nonhealing ulcers. Some 20 of 21 patients in group 3 (0.04% [wt/wt] hEGF) showed complete wound healing. Healing rates were 42.10, 57.14, and 95% for the control, 0.02% (wt/wt) hEGF, and 0.04% (wt/wt) hEGF groups, respectively. Kaplan-Meier survival analysis suggested that application of cream with 0.04% (wt/wt) hEGF caused more ulcers to heal by 12 weeks and increased the rate of healing compared with the other treatments (log-rank test, P = 0.0003).

CONCLUSIONS—Our data support the contention that application of hEGF-containing cream, in addition to good foot care from a multidisciplinary team, significantly enhances diabetic foot ulcer wound healing and reduces the healing time.
Percent Change in Wound Area of Diabetic Foot Ulcers Over a 4-Week Period Is a Robust Predictor of Complete Healing in a 12-Week Prospective Trial
Authors: Sheehan Peter , Jones Peter , Caselli Antonella , Giurini John M. , Veves Aristidis
Published: March 2007

OBJECTIVE—To assess the ability of the 4-week healing rate to predict complete healing over a 12-week period in a large prospective multicenter trial of diabetic patients with foot ulceration.

RESEARCH DESIGN AND METHODS—We examined the change in ulcer area over a 4-week period as a predictor of wound healing within 12 weeks in patients who were seen weekly in a prospective, randomized controlled trial.

RESULTS—Wound area measurements at baseline and after 4 weeks were performed in 203 patients. The midpoint between the percentage area reduction from baseline at 4 weeks in patients healed versus those not healed at 12 weeks was found to be 53%. Subjects with a reduction in ulcer area greater than the 4-week median had a 12-week healing rate of 58%, whereas those with reduction in ulcer area less than the 4-week median had a healing rate of only 9% (P < 0.01). The absolute change in ulcer area at 4 weeks was significantly greater in healers versus nonhealers (1.5 vs. 0.8 cm2, P < 0.02). The percent change in wound area at 4 weeks in those who healed was 82% (95% CI 70–94), whereas in those who failed to heal, the percent change in wound area was 25% (15–35; P < 0.001).

CONCLUSIONS—The percent change in foot ulcer area after 4 weeks of observation is a robust predictor of healing at 12 weeks. This simple tool may serve as a pivotal clinical decision point in the care of diabetic foot ulcers for early identification of patients who may not respond to standard care and may need additional treatment.
Cutaneous Blood Flow in Type 2 Diabetic Individuals After an Acute Bout of Maximal Exercise
Authors: Colberg Sheri R. , Parson Henri K. , Holton D. Robb , Nunnold Tanja , Vinik Aaron I.
Published: March 2007

OBJECTIVE—We previously demonstrated a positive association between chronic aerobic exercise and dorsal foot skin blood flow during local heating in type 2 diabetic individuals. Thus, we hypothesized that a prior acute bout of maximal exercise would also have positive effects on postexercise blood flow.

RESEARCH DESIGN AND METHODS—Subjects consisted of 32 individuals with type 2 diabetes and 26 nondiabetic control subjects further subdivided based on their physical activity status: diabetic exerciser (DE), diabetic sedentary (DS), control exerciser (CE), or control sedentary. Dorsal foot cutaneous blood flow was measured noninvasively by continuous laser-Doppler assessment at baseline and during local heating to 44°C before and after a maximal bout of cycle exercise. Interstitial nitric oxide (NO) levels were measured concurrently in the foot dorsum.

RESULTS—Increases in blood flow and its responsiveness to local heating to 44°C were significantly lower in both diabetic groups compared with CE before maximal exercise, but perfusion responsiveness remained lower in DS subjects only after exercise (P < 0.05). Baseline skin blood flow was not different among groups preexercise, but it was significantly increased postexercise in DE subjects only. Interstitial NO levels were not significantly different at either time. At baseline, groups differed only in HbA1c, fasting serum glucose, HDL cholesterol, and insulin resistance (homeostasis model assessment method).

CONCLUSIONS—All diabetic individuals exhibit a blunted responsiveness of cutaneous blood flow with local heating to 44°C before maximal exercise compared with active nondiabetic individuals, but after an exercise bout, it remains significantly blunted only in diabetic individuals who are sedentary. These findings occur independently of changes in interstitial NO levels.
The Epidemiology of Diabetes in the Manitoba-Registered First Nation Population
Authors: Green Chris , Blanchard James F. , Young T. Kue , Griffith Jane
Published: March 2007

OBJECTIVE—This study provides an overview of the epidemiology of diabetes in the Manitoba First Nation population.

RESEARCH DESIGN AND METHODS—The study uses data derived from the population-based Manitoba Diabetes Database to compare the demographic and geographic patterns of diabetes in the Manitoba First Nation population to the non–First Nation population.

RESULTS—Although the prevalence of diabetes rose steadily in both the First Nation and the non–First Nation populations between 1989 and 1998, the epidemiological pattern of diabetes in these two populations differed significantly. The First Nation population was observed to have age-standardized incidence and prevalence rates of diabetes up to 4.5 times higher than those found in the non–First Nation population. The sex ratio and the geographic patterning of diabetes incidence and prevalence in the two study populations were reversed.

CONCLUSIONS—The results of the study suggest that diabetes prevalence will likely continue to rise in the Manitoba First Nation population into the foreseeable future, and that the impact of this rising diabetes prevalence can only be effectively managed through a population-based public health approach focusing on primary and secondary prevention. The dramatically higher rates of diabetes in Manitoba First Nation population as compared with the non–First Nation population highlight the urgency of this activity. These prevention efforts need to be supported by further research into the reasons for the unique epidemiological patterns of diabetes incidence and prevalence in the First Nation population observed in this study. These include investigating why First Nation populations living in the Northern areas of the province seem to be protected from developing high rates of diabetes and why First Nation women experience much higher rates of the disease.
A Population Perspective on Diabetes Prevention
Authors: Burke James P. , Williams Ken , Narayan K.M. Venkat , Leibson Cynthia , Haffner Steven M. , Stern Michael P.
Published: March 2007

OBJECTIVE—To examine the influence of obesity and prevention of weight gain on the incidence of type 2 diabetes.

RESEARCH DESIGN AND METHODS—We examined participants in the San Antonio Heart Study, a prospective population-based study of Mexican Americans and non-Hispanic whites residing in San Antonio, Texas. BMI was stratified into four categories: normal (<25 kg/m2), overweight (≥25 kg/m2 and <30 kg/m2), obese (≥30 kg/m2 and <35 kg/m2), and very obese (≥35 kg/m2). The number and proportion of incident cases prevented by targeting each BMI category were estimated. In addition, we calculated the decrease in risk of developing type 2 diabetes associated with weight gain prevention across both the BMI and age spectra.

RESULTS—Preventing normal individuals from becoming overweight would result in the greatest reduction in incidence of type 2 diabetes. This would result in a 62 and 74% reduction in the incidence of type 2 diabetes in Mexican Americans and non-Hispanic whites, respectively. Preventing the entire population from gaining, on average, 1 BMI unit would result in a reduction in incidence of type 2 diabetes of 12.4 and 13.0% in Mexican Americans and non-Hispanic whites, respectively.

CONCLUSIONS—The majority of cases of type 2 diabetes were in individuals who were overweight or mildly obese with a family history of type 2 diabetes. Public health resources should be directed toward the prevention of weight gain among normal and overweight individuals in order to prevent the maximum number of cases of type 2 diabetes.
Lack of Acculturation Is a Risk Factor for Diabetes in Arab Immigrants in the U.S.
Authors: Jaber Linda A. , Brown Morton B. , Hammad Adnan , Zhu Qian , Herman William H.
Published: March 2007

OBJECTIVE—To examine the relationship between dysglycemia (impaired fasting glucose, impaired glucose tolerance, and diabetes) and acculturation, physical activity, and perceived stress in Arab immigrants in the U.S.

RESEARCH DESIGN AND METHODS—In a cross-sectional population-based study, we examined 520 Arab Americans, aged 20–75 years, who were born in the Middle East and immigrated to southeastern Michigan. Dysglycemia was assessed by history and with a 2-h 75-g oral glucose tolerance test. Acculturation, physical activity, and perceived stress were measured with standardized questionnaires.

RESULTS—Associations were found between dysglycemia in men and older age at immigration, unemployment, speaking Arabic with friends, being less active in Arabic organizations, more frequent consumption of Arabic food, and less integration into American society. Dysglycemia in women was associated with being raised in rural areas of the Middle East, older age at immigration, longer length of stay in the U.S., not being employed outside the home, less than high school education, not attending Arabic or American schools, and not being able to read Arabic. Among men, older age at immigration, shorter length of stay in the U.S., less activity in Arab organizations, and eating Arabic food were associated with dysglycemia independent of age and BMI. Among women, acculturation was very low and was confounded with age and BMI as powerful risk factors for dysglycemia. No association was found between physical activity, perceived stress, and the risk of dysglycemia in either sex.

CONCLUSIONS—Lack of acculturation is an important risk factor for dysglycemia in immigrant Arab Americans. Intervention programs aimed at diabetes prevention should consider the acculturation process.
Decreased Serum Levels of Adiponectin Are a Risk Factor for the Progression to Type 2 Diabetes in the Japanese Population
Authors: Daimon Makoto , Oizumi Toshihide , Saitoh Tamotsu , Kameda Wataru , Hirata Akihiko , Yamaguchi Hiroshi , Ohnuma Hiroshi , Igarashi Masahiko , Tominaga Makoto , Kato Takeo
Published: March 2007

OBJECTIVE—To examine whether decreased serum levels of adiponectin are an independent risk factor for the progression to type 2 diabetes in a Japanese population.

RESEARCH DESIGN AND METHODS—The serum levels of adiponectin and tumor necrosis factor-α (TNF-α) at baseline (from 1995 to 1997) were evaluated in 1,792 individuals (1,023 women and 769 men, aged 58.5 ± 12.5 years) from a cohort population (n = 3,706) of the Funagata study. Glucose tolerance was evaluated at baseline and also at 5-year follow-up examinations (n = 978, follow-up rate, 54.6%) according to the 1985 World Health Organization criteria. The correlation of clinical traits with serum levels of adiponectin was examined. The association of the traits with the progression to type 2 diabetes at the 5-year follow-up was also examined.

RESULTS—Among the traits examined, the correlation with aging was highest (r = 0.312, P < 0.001). Eighteen subjects with normal glucose tolerance (NGT) developed diabetes, and 709 remained NGT at the 5-year follow-up examinations. The subjects who became diabetic had decreased serum levels of adiponectin (7.29 ± 2.35 vs. 9.13 ± 2.35 10 × log μg/ml, P = 0.009). Multiple logistic regression analysis with age, sex, waist-to-hip ratio, and 2-h plasma glucose as the variables revealed that serum adiponectin level (odds ratio [per 0.1 log μg/ml] 0.766, P = 0.029) was an independent risk factor for the progression to type 2 diabetes. The subjects whose serum levels of adiponectin were in the lowest tertile were 9.320 times (95% CI 1.046–83.1) more likely to develop diabetes than those in the highest tertile (P = 0.046).

CONCLUSIONS—Decreased serum adiponectin level is an independent risk factor for progression to type 2 diabetes.