bluuebunny/crossref_metadata_2025 huggingface dataset:
Dietary Fats Do Not Contribute to Hyperlipidemia in Children and Adolescents With Type 1 Diabetes
Authors: Wiltshire Esko J. , Hirte Craig , Couper Jennifer J.
Published: March 2007

OBJECTIVE—To determine the relative influence of diet, metabolic control, and familial factors on lipids in children with type 1 diabetes and control subjects.

RESEARCH DESIGN AND METHODS—We assessed fasting serum cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, lipoprotein(a), apolipoprotein (apo)-A1, and apoB in 79 children and adolescents with type 1 diabetes and 61 age- and sex-matched control subjects, together with dietary intakes using a quantitative food frequency questionnaire.

RESULTS—Total cholesterol, LDL cholesterol, apoB, HDL cholesterol, and apoA1 were significantly higher in children with diabetes. Children with diabetes had higher percentage energy intake from complex carbohydrates (P = 0.001) and fiber intake (P = 0.02), and they had lower intake of refined sugar (P < 0.001) and percentage energy from saturated fat (P = 0.045) than control subjects. Total cholesterol (β = 0.43, P < 0.001), LDL cholesterol (β = 0.4, P < 0.001), and apoB (β = 0.32, P = 0.006) correlated independently with HbA1c but not dietary intake. HDL cholesterol (β = 0.24, P = 0.05) and apoA1 (β = 0.32, P = 0.004) correlated independently with HbA1c, and HDL cholesterol (β = −0.34, P = 0.009) correlated with percentage energy intake from complex carbohydrates. Triglycerides correlated independently with percentage energy intake from complex carbohydrates (β = 0.33, P = 0.01) and insulin dose (β = 0.26, P = 0.04). Subjects with diabetes and elevated LDL (>3.35 mmol/l, >130 mg/dl), for whom dietary therapy would be recommended, had significantly higher HbA1c (P = 0.007), but they had higher intake of complex carbohydrates than subjects with LDL cholesterol <3.35 mmol/l.

CONCLUSIONS—Lipid abnormalities remain common in children and adolescents with type 1 diabetes who adhere to current dietary recommendations, and they relate to metabolic control but not dietary intake.
Diabetic Foot Syndrome
Authors: Lavery Lawrence A. , Armstrong David G. , Wunderlich Robert P. , Tredwell Jeffrey , Boulton Andrew J.M.
Published: March 2007

OBJECTIVE—To report the incidence of diabetes-related lower-extremity complications in a cohort of patients enrolled in a diabetes disease management program.

RESEARCH DESIGN AND METHODS—We evaluated screening results and clinical outcomes for the first 1,666 patients enrolled in a disease management program for a period of 24 months (50.3% men, aged 69.1 ± 11.1 years).

RESULTS—The incidence of ulceration, infection, amputation, and lower-extremity bypass was 68.4, 36.5, 5.9, and 7.7 per 1,000 persons with diabetes per year. Amputation incidence was higher in Mexican Americans than in non-Hispanic whites (7.4/1,000 vs. 4.1/1,000; P = 0.003, odds ratio [OR] 1.8, 95% CI 1.2–2.7). The amputation-to-ulcer ratio was 8.7%. The incidence of Charcot arthropathy was 8.5/1,000 per year. Charcot was more common in non-Hispanic whites than in Mexican Americans (11.7/1,000 vs. 6.4/1,000; P = 0.0001, 1.8, 1.3–2.5). The prevalence of peripheral vascular disease was 13.5%, with no significant difference based on ethnicity (P = 0.3). There was not a significant difference in incidence of foot infection (P = 0.9), lower-extremity bypass (P = 0.3), or ulceration (P = 0.1) based on ethnicity. However, there were more failed bypasses in Mexican Americans (33%) than in non-Hispanic whites (7.1%). Mexican Americans were 3.8 times more likely to have a failed bypass (leading to an amputation) or be diagnosed as “nonbypassable” than non-Hispanic whites (75.0 vs. 44.0%; P = 0.01, 3.8, 1.2–11.8).

CONCLUSIONS—The incidence of amputation is higher in Mexican Americans, despite rates of ulceration, infection, vascular disease, and lower-extremity bypass similar to those of non-Hispanic whites. There may be factors associated with failed or failure to bypass that mandate further investigation.
Dermatophyte Test Medium Culture for Evaluating Toenail Infections in Patients With Diabetes
Authors: Rich Phoebe , Harkless Lawrence B. , Atillasoy Ercem S.
Published: March 2007

OBJECTIVE—To evaluate the performance of the in-office dermatophyte test medium (DTM) culture when used to confirm the diagnosis of onychomycosis in diabetic patients.

RESEARCH DESIGN AND METHODS—Nail samples from 184 diabetic patients who exhibited symptoms consistent with toenail onychomycosis were screened for dermatophyte fungal infection using DTM, potassium hydroxide evaluation, and central mycology laboratory culture tests. The diabetic patient group investigated in this study is a subset of a heterogeneous set of patients who participated in a nationwide survey designed to investigate the use of fungal culture tests by dermatologists, podiatrists, and primary care physicians described in detail elsewhere. The overall sensitivity of the DTM and central laboratory culture methods was estimated and compared. Sensitivity differences between DTM and central laboratory culture methods were tested for statistical significance using the McNemar statistic.

RESULTS—DTM culture was positive in 102 of 184 patients (55%), while the central laboratory culture test detected the existence of fungal infection in 78 of 184 (42%). The two tests were in agreement (both positive or both negative) in 114 of 184 patients (62%). Central laboratory culture identified dermatophytes as the pathogen in 91% of positive cases.

CONCLUSIONS—DTM is a convenient and inexpensive culture test that can be used to confirm dermatophyte infections in diabetic patients with presumed onychomycosis. We found this test to be well suited for use in the primary care setting. Because oral antifungal agents are effective against dermatophyte species, which cause the vast majority of nail infections, diagnosis of onychomycosis requires confirmation of dermatophyte infection only, not identification of genus and species. DTM fulfills this requirement and has a diagnostic yield comparable to central laboratory culture.
Weight Loss in Combination With Physical Activity Improves Endothelial Dysfunction in Human Obesity
Authors: Sciacqua Angela , Candigliota Mafalda , Ceravolo Roberto , Scozzafava Angela , Sinopoli Flora , Corsonello Andrea , Sesti Giorgio , Perticone Francesco
Published: March 2007

OBJECTIVE—To test whether weight loss may improve endothelial dysfunction in human obesity, we recruited 28 healthy obese subjects, aged 30–46 years, with BMI 30–43 kg/m2.

RESEARCH DESIGN AND METHODS—Endothelium-dependent and -independent vasodilation were investigated by intra-arterial infusion of increasing doses of acetylcholine (ACh; 7.5, 15, and 30 μg · ml−1 · min−1) and sodium nitroprusside (0.8, 1.6, and 3.2 μg · ml−1 · min−1). Insulin resistance was estimated by homeostasis model assessment (HOMA). Weight loss was obtained by caloric restriction and physical activity.

RESULTS—We observed a significant reduction in BMI (from 33.1 ± 4.2 to 27.5 ± 4.5 kg/m2, −16.9%, P < 0.0001) and in waist circumference (from 108.2 ± 12.1 to 96.8 ± 12.9 cm, −10.5%, P < 0.0001). Weight loss was also associated with a significant increase in ACh-stimulated forearm blood flow (FBF), from 7.4 ± 2.8 to 12.9 ± 3.4 ml · 100 ml−1 of tissue · min−1 kg/m2 (P < 0.0001). Multivariate regression analysis demonstrated that the only independent predictor of FBF was HOMA, accounting for 44.5% of the variation, whereas the addition of BMI explained another 2.3% of the variation.

CONCLUSIONS—Our data demonstrate that energy-restricted diet associated with physical activity induce a significant and clinically relevant improvement in ACh-stimulated vasodilation in obese healthy subjects.
Racial Differences in Glycemic Control in a Well-Functioning Older Diabetic Population
Authors: de Rekeneire Nathalie , Rooks Ronica N. , Simonsick Eleanor M. , Shorr Ronald I. , Kuller Lewis H. , Schwartz Ann V. , Harris Tamara B.
Published: March 2007

OBJECTIVE—To evaluate racial differences and factors associated with worse glycemic control in well-functioning older individuals with type 2 diabetes. Our hypothesis was that glycemic control would be worse among black than white diabetic individuals but that this association would be explained by differences in severity of diabetes, health status, health care indicators, and social, psychological, or behavorial factors. We further hypothesized that the association of race with poorer glycemic control would be limited to those with lower education or lower income.

RESEARCH DESIGN AND METHODS—Cross-sectional analysis of 468 diabetic participants among a cohort of 3,075 nondisabled blacks and whites aged 70–79 years living in the community enrolled in the Health, Aging and Body Composition Study. Glycemic control was measured by the level of HbA1c.

RESULTS—A total of 58.5% of the diabetic individuals were black. Although control was poor in all diabetic participants (HbA1c ≥7% in 73.7%), blacks had worse glycemic control than whites (age- and sex-adjusted mean HbA1c, 8.4% in blacks and 7.4% in whites; P < 0.01). Race differences in glycemic control remained significant, even after adjusting for current insulin therapy, cardiovascular disease, higher total cholesterol, and not receiving a flu shot in the previous year, all of which were associated with higher HbA1c concentrations. Controlling for these factors reduced the association by 27%. Race remained an important factor in glycemic control, even when results were stratified by education or income.

CONCLUSIONS—HbA1c concentrations were higher in older black diabetic individuals. Differences in glycemic control by race were associated with disease severity, health status, and poorer quality of care, but these factors did not fully explain the higher HbA1c levels in older black diabetic individuals.
Effects of Metformin and Rosiglitazone Monotherapy on Insulin-Mediated Hepatic Glucose Uptake and Their Relation to Visceral Fat in Type 2 Diabetes
Authors: Iozzo Patricia , Hallsten Kirsti , Oikonen Vesa , Virtanen Kirsi A. , Parkkola Riitta , Kemppainen Jukka , Solin Olof , Lonnqvist Fredrik , Ferrannini Ele , Knuuti Juhani , Nuutila Pirjo
Published: March 2007

OBJECTIVE—Impaired insulin-mediated hepatic glucose uptake (HGU) has been implicated in the hyperglycemia of type 2 diabetes. We examined the effects of metformin (2 g/day) and rosiglitazone (8 mg/day) monotherapy on HGU and its relation to subcutaneous fat, visceral fat (VF), and whole-body insulin-mediated glucose metabolism in type 2 diabetic patients.

RESEARCH DESIGN AND METHODS—Glucose uptake was measured before and after 26 weeks of treatment using positron emission tomography with [18F]2-fluoro-2-deoxyglucose during euglycemic hyperinsulinemia; fat depots were quantified by magnetic resonance imaging.

RESULTS—Fasting plasma glucose levels were significantly decreased after either rosiglitazone (−0.9 ± 0.5 mmol/l) or metformin treatment (−1.1 ± 0.5 mmol/l) in comparison with placebo; only metformin was associated with weight loss (P < 0.02 vs. placebo). When controlling for the latter, the placebo-subtracted change in whole-body glucose uptake averaged −1 ± 4 μmol · min−1 · kg−1 in metformin-treated patients (NS) and +9 ± 3 μmol · min−1 · kg−1 in rosiglitazone-treated patients (P = 0.01). Both rosiglitazone and metformin treatment were associated with an increase in HGU; versus placebo, the change reached statistical significance when controlling for sex (placebo-subtracted values = +0.008 ± 0.004 μmol · min−1 · kg−1 · pmol/l−1, P < 0.03, for metformin; and +0.007 ± 0.004, P < 0.07, for rosiglitazone). After treatment with either drug, insulin-mediated VF glucose uptake (VFGU) was higher than with placebo. In the whole dataset, changes in HGU were negatively related to changes in HbA1c (r = 0.43, P = 0.01) and positively associated with changes in VFGU (r = 0.48, P < 0.01).

CONCLUSIONS—We conclude that both metformin and rosiglitazone monotherapy increase HGU in type 2 diabetes; direct drug actions, better glycemic control, and enhanced VF insulin sensitivity are likely determinants of this phenomenon.
Adiponectin Is Present in Cord Blood but Is Unrelated to Birth Weight
Authors: Lindsay Robert S. , Walker James D. , Havel Peter J. , Hamilton Barbara A. , Calder Andrew A. , Johnstone Frank D. ,   on behalf of The Scottish Multicentre Study of Diabetes in Pregnancy
Published: March 2007

OBJECTIVE—In adults, adiponectin is reduced in association with excess adiposity, type 2 diabetes, and hyperinsulinemia. We assessed whether adiponectin was 1) present in the fetal circulation, 2) altered in the fetal circulation in the presence of maternal diabetes, and 3) had relations to fetal cord blood insulin or adiposity.

RESEARCH DESIGN AND METHODS—We assessed adiponectin in cord blood in a large cohort of singleton offspring of diabetic mothers (ODM; n = 134) and control mothers (n = 45).

RESULTS—Adiponectin was present in cord blood and, in ODM, was higher in those delivered at later gestational ages (Spearman r = 0.18, P = 0.03). Adiponectin was slightly lower in ODM than control subjects (ODM 19.7 ± 6.1 vs. control 21.8 ± 5.3 μg/ml; P = 0.04), although this difference could potentially reflect different gestational ages in the two groups (ODM 37.6 ± 1.5 and control 40.1 ± 1.1 weeks). In contrast to adults, adiponectin levels in the fetus were unrelated to the degree of adiposity, blood insulin, or leptin in either control subjects or ODM.

CONCLUSIONS—Adiponectin is present in cord blood but does not show expected physiological relations with adiposity as observed in adults.
The Direct Medical Cost of Type 2 Diabetes
Authors: Brandle Michael , Zhou Honghong , Smith Barbara R.K. , Marriott Deanna , Burke Ray , Tabaei Bahman P. , Brown Morton B. , Herman William H.
Published: March 2007

OBJECTIVE—To describe the direct medical costs associated with type 2 diabetes, as well as its treatments, complications, and comorbidities.

RESEARCH DESIGN AND METHODS—We studied a random sample of 1,364 subjects with type 2 diabetes who were members of a Michigan health maintenance organization. Demographic characteristics, duration of diabetes, diabetes treatments, glycemic control, complications, and comorbidities were assessed by surveys and medical chart reviews. Annual resource utilization and costs were assessed using health insurance claims. The log-transformed annual direct medical costs were fitted by multiple linear regression to indicator variables for demographics, treatments, glycemic control, complications, and comorbidities.

RESULTS—The median annual direct medical costs for subjects with diet-controlled type 2 diabetes, BMI 30 kg/m2, and no microvascular, neuropathic, or cardiovascular complications were $1,700 for white men and $2,100 for white women. A 10-kg/m2 increase in BMI, treatment with oral antidiabetic or antihypertensive agents, diabetic kidney disease, cerebrovascular disease, and peripheral vascular disease were each associated with 10–30% increases in cost. Insulin treatment, angina, and MI were each associated with 60–90% increases in cost. Dialysis was associated with an 11-fold increase in cost.

CONCLUSIONS—Insulin treatment and diabetes complications have a substantial impact on the direct medical costs of type 2 diabetes. The estimates presented in this model may be used to analyze the cost-effectiveness of interventions for type 2 diabetes.
Diabetes and Driving Mishaps
Authors: Cox Daniel J. , Penberthy Jennifer Kim , Zrebiec John , Weinger Katie , Aikens James E. , Frier Brian , Stetson Barbara , DeGroot Mary , Trief Paula , Schaechinger Hartmut , Hermanns Norbert , Gonder-Frederick Linda , Clarke William
Published: March 2007

OBJECTIVE—The intensive treatment of diabetes to achieve strict glycemic control is a common clinical goal, but it is associated with an increased incidence of hypoglycemia. Becoming hypoglycemic while driving is a hazardous condition and may lead to a greater incidence of driving mishaps. This study investigated whether diabetes is associated with increased risk of driving mishaps and correlates of such a relationship.

RESEARCH DESIGN AND METHODS—During routine visits to diabetes specialty clinics in seven U.S. and four European cities, consecutive adults with type 1 diabetes, type 2 diabetes, and nondiabetic spouse control subjects (n = 341, 332, and 363, respectively) completed an anonymous questionnaire concerning diabetes and driving.

RESULTS—Type 1 diabetic drivers reported significantly more crashes, moving violations, episodes of hypoglycemic stupor, required assistance, and mild hypoglycemia while driving as compared with type 2 diabetic drivers or spouse control subjects (P < 0.01–0.001). Type 2 diabetic drivers had driving mishap rates similar to nondiabetic spouses, and the use of insulin or oral agents for treatment had no effect on the occurrence of driving mishaps. Crashes among type 1 diabetic drivers were associated with more frequent episodes of hypoglycemic stupor while driving, less frequent blood glucose monitoring before driving, and the use of insulin injection therapy as compared with pump therapy. One-half of the type 1 diabetic drivers and three-quarters of the type 2 diabetic drivers had never discussed hypoglycemia and driving with their physicians.

CONCLUSIONS—Type 1 diabetic drivers are at increased risk for driving mishaps, but type 2 diabetic drivers, even on insulin, appear not to be at a higher risk than nondiabetic individuals. Clinical and treatment factors appear to increase risk, e.g., more frequent hypoglycemia while driving, method of insulin delivery, and infrequent self-testing before driving. Physicians are encouraged to talk to their type 1 diabetic patients about hypoglycemia and driving.
Fulminant Type 1 Diabetes
Authors: Imagawa Akihisa , Hanafusa Toshiaki , Uchigata Yasuko , Kanatsuka Azuma , Kawasaki Eiji , Kobayashi Tetsuro , Shimada Akira , Shimizu Ikki , Toyoda Tetsuya , Maruyama Taro , Makino Hideichi
Published: March 2007

OBJECTIVE— To describe the clinical and immunologic characteristics of fulminant type 1 diabetes, a novel subtype of type 1 diabetes, we conducted a nationwide survey.

RESEARCH DESIGN AND METHODS—History and laboratory data, including islet-related autoantibodies, were examined in 222 patients with fulminant and nonfulminant type 1 diabetes in our hospitals in addition to another 118 patients with fulminant type 1 diabetes located outside our hospitals in Japan.

RESULTS—In our hospitals, of the 222 patients studied, 43 (19.4%) were diagnosed with fulminant type 1 diabetes, 137 (61.7%) were classified as having autoimmune type 1 diabetes, and 42 were type 1 diabetic subjects who were not fulminant and did not have anti-islet antibodies. An additional 118 fulminant patients outside our hospitals were enrolled, making a total of 161 fulminant type 1 diabetic subjects (83 male and 78 female subjects; 14 children/adolescents and 147 adults) identified from all over Japan. (In 2000, the average incidence was three cases per month.) Flu-like symptoms and pregnancy were more frequently observed in the fulminant than in the autoimmune group (P < 0.001). In the fulminant patients, 4.8% were positive for anti-GAD antibodies and none were positive for anti–islet antigen 2 antibodies.

CONCLUSIONS—Fulminant type 1 diabetes is a distinct subtype and accounts for ∼20% of the ketosis-onset type 1 diabetes cases in Japan. Flu-like symptoms are characteristic of disease onset. Metabolic derangement is more severe in this subtype than in autoimmune type 1 diabetes.
Plasma Adiponectin and Leptin Levels, Body Composition, and Glucose Utilization in Adult Women With Wide Ranges of Age and Obesity
Authors: Ryan Alice S. , Berman Dora M. , Nicklas Barbara J. , Sinha Madhur , Gingerich Ronald L. , Meneilly Grady S. , Egan Josephine M. , Elahi Dariush
Published: March 2007

OBJECTIVE—The purpose of this study was to determine the relationships between plasma adiponectin and leptin levels, total and central obesity, and glucose utilization across the adult age span.

RESEARCH DESIGN AND METHODS—We studied 148 women aged 18–81 years with a BMI range of 17.2–44.3 kg/m2. Total percent body fat was determined by dual-energy X-ray absorptiometry and abdominal fat by computed tomography. Glucose tolerance in non-type 2 diabetic volunteers was determined with an oral glucose tolerance test. Glucose utilization (M) was measured during the last 60 min of hyperinsulinemic-euglycemic clamps (240 pmol · m−2 · min−1). Plasma adiponectin levels were measured by radioimmunoassay. The women were separated into three age-groups: young, middle, and old (<40, 40–59, and ≥60 years, respectively), as well as by glucose tolerance status.

RESULTS—Adiponectin concentrations did not differ by age-groups. There were significant age effects for BMI, percent body fat, visceral fat, subcutaneous abdominal fat, Vo2max, and M. Adiponectin levels were lower in the prediabetic women (n = 18) than in the normal glucose-tolerant women (n = 108) and the women with type 2 diabetes (n = 22) (both P < 0.05). Univariate correlations revealed significant negative relationships between plasma adiponectin levels and BMI, percent body fat, visceral fat, subcutaneous abdominal fat, fasting leptin, and fasting insulin and positive relationship with M (all P < 0.05). In a multiple stepwise regression model to predict adiponectin, only M remained in the model at P < 0.001. Multivariate analyses revealed a significant relation for M as a function of adiponectin, insulin, and Vo2max.

CONCLUSIONS—The data suggest that plasma adiponectin does not change with age but levels are negatively associated with percent body fat, visceral fat, subcutaneous abdominal fat, insulin, and leptin levels in women. Adiponectin is positively associated with M across the age span in women.
Optimal Blood Glucose Control During 18 Years Preserves Peripheral Nerve Function in Patients With 30 Years’ Duration of Type 1 Diabetes
Authors: Larsen Jakob R. , Sjoholm Hans , Hanssen Kristian F. , Sandvik Leiv , Berg Tore J. , Dahl-Jorgensen Knut
Published: March 2007

OBJECTIVE—To assess the association between 18 years of mean HbA1c and nerve conduction parameters of the lower limb in patients with type 1 diabetes of 30 years’ duration.

RESEARCH DESIGN AND METHODS—HbA1c has been examined prospectively since 1982 in a group of 39 patients with type 1 diabetes. Mean age at baseline was 25 years (range 18–40) with 12 years’ disease duration. The mean age at diagnosis of diabetes was 12.5 years. Nerve function of lower limbs was assessed at baseline, after 8 years, and after 18 years.

RESULTS—A total of 23 men and 16 women were studied. Mean age was 43 years. Mean HbA1c was 8.2% (range 6.6–11.3) during 18-year follow-up. Nerve conduction velocity (NCV) and nerve action potential amplitude (NAPA) at the last examination were significantly associated with mean HbA1c (P < 0. 05). From 1982 to 1999, there was a significant reduction in nerve function in patients with mean HbA1c ≥8.4% (highest tertile). For example, the mean NCV in the tibial nerve was reduced from 47 to 31 m/s (P < 0.01). The number of nerves with NCV (P < 0.01) and NAPA (P = 0.01) reduced to below the reference level in each patient was also significantly associated to mean HbA1c. No significant associations were found between nerve function parameters, sex, disease duration, blood pressure, serum cholesterol, microalbuminuria, or smoking.

CONCLUSIONS—The present study shows that mean HbA1c is a strong predictor of nerve function. Mean HbA1c <8.4% over 18 years was associated with near-normal nerve function.
ACE Inhibitors Improve Diabetic Nephropathy Through Suppression of Renal MCP-1
Authors: Amann Berthold , Tinzmann Ralph , Angelkort Bernhard
Published: March 2007

OBJECTIVE—Chemokines play an important role in the pathogenesis of diabetic nephropathy. Angiotensin II induces several fibrogenic chemokines, namely monocyte chemoattractant protein-1 (MCP-1) and transforming growth factor-β. The progression of diabetic nephropathy can be retarded by ACE inhibitors (ACEIs) in patients with type 1 and type 2 diabetes. We examined if blockade of the renin-angiotensin system lowered urinary levels of the chemokine MCP-1 and correlated urinary MCP-1 (uMCP-1) with parameters of renal function and glucose and lipid metabolism before and after 1 year of treatment with an ACE inhibitor.

RESEARCH DESIGN AND METHODS—In 22 patients with type 2 diabetes and diabetic nephropathy in stages 3–5, treatment with the ACEI lisinopril was initiated. Before treatment and after 12 months of continuous therapy, proteinuria, creatinine clearance, uMCP-1 levels, BMI, HbA1c, and serum cholesterol were assessed.

RESULTS—Lisinopril treatment improved renal function. Proteinuria decreased from 410 ± 662 mg per 24 h to 270 ± 389 mg per 24 h. Creatinine clearance rose from 61 ± 26 to 77 ± 41 ml/min. Urinary MCP-1 levels decreased from 0.456 ± 0.22 ng/mg creatinine to 0.08 ± 0.096 ng/mg creatinine. The change in uMCP-1 correlated significantly (r = 0.61, P < 0.001) with the change in proteinuria. No other parameter correlated with the improvement in renal function.

CONCLUSIONS—Blockade of the renin-angiotensin system in type 2 diabetic patients with diabetic nephropathy reduces uMCP-1 levels and improves renal function. Because MCP-1 induces monocyte immigration and differentiation to macrophages, which augment extracellular matrix production and tubulointerstitial fibrosis, pharmacological reduction of angiotensin II may also exert its beneficial effects in diabetic nephropathy by downregulation of renal MCP-1.
Costs of Screening for Pre-diabetes Among U.S. Adults
Authors: Zhang Ping , Engelgau Michael M. , Valdez Rodolfo , Benjamin Stephanie M. , Cadwell Betsy , Venkat Narayan K.M.
Published: March 2007

OBJECTIVE—We evaluated various strategies to identify individuals aged 45–74 years with pre-diabetes (either impaired glucose tolerance or impaired fasting glucose).

RESEARCH DESIGN AND METHODS—We conducted a cost analysis to evaluate the effectiveness (proportion of cases identified), total costs, and efficiency (cost per case identified) of five detection strategies: an oral glucose tolerance test (OGTT), a fasting plasma glucose (FPG) test, an HbA1c test, a capillary blood glucose (CBG) test, and a risk assessment questionnaire. For the first strategy, all individuals received an OGTT. For the last four strategies, only those with a positive screening test received an OGTT. Data were from the Third U.S. National Health and Nutrition Examination Survey, 2000 census, Medicare, and published literature. One-time screening costs were estimated from both a single-payer perspective and a societal perspective.

RESULTS—The proportion of pre-diabetes and undiagnosed diabetes identified ranged from 69% to 100% (12.1–17.5 million). The cost per case identified ranged from $176 to $236 from a single-payer perspective and from $247 to $332 from a societal perspective. Testing all with OGTT was the most effective strategy, but the CBG test and risk assessment questionnaire were the most efficient. If people are substantially less willing to take an OGTT than a FPG test, then the FPG testing strategy was the most effective strategy.

CONCLUSIONS—There is a tradeoff between effectiveness and efficiency in choosing a strategy. The most favorable strategy depends on if the goal of the screening program is to identify more cases or to pursue the lowest cost per case. The expected percentage of the population willing to take an OGTT is also a consideration.
Urinary Connective Tissue Growth Factor Excretion in Patients With Type 1 Diabetes and Nephropathy
Authors: Gilbert Richard E. , Akdeniz Aysel , Weitz Stephen , Usinger William R. , Molineaux Christopher , Jones Susan E. , Langham Robyn G. , Jerums George
Published: March 2007

OBJECTIVE—Excretion of growth factors in the urine has been implicated in the pathogenesis of tubulointerstitial disease that characterizes proteinuric renal disease. In this cross-sectional study, we sought to examine the urinary excretion of the profibrotic cytokine connective tissue growth factor (CTGF) in type 1 diabetic patients with incipient and overt diabetic nephropathy.

RESEARCH DESIGN AND METHODS—We recruited 31 subjects with type 1 diabetes from a hospital diabetes outpatient clinic. Of these, 10 subjects were normoalbuminuric, 8 were microalbuminuric and not receiving ACE inhibitor treatment, and 13 were macroalbuminuric, 8 of whom were receiving ACE inhibitor treatment. Urinary CTGF NH2-terminal fragment (CTGF-N) was determined by enzyme-linked immunosorbent assay and expressed relative to urinary creatinine.

RESULTS—Urinary CTGF-N was closely correlated with the degree of albuminuria (r = 0.76, P < 0.001). In comparison with normoalbuminuric subjects, urinary CTGF-N was increased 10- and 100-fold in micro- and untreated macroalbuminuric subjects, respectively (CTGF-N–to–creatinine ratio: normoalbuminuria 0.23 ×/÷ 1.3 ng/mg, microalbuminuria 2.1 ×/÷ 1.7 ng/mg, untreated macroalbuminuria 203 ×/÷ 3.8 ng/mg, and geometric mean ×/÷ tolerance factor; P < 0.05 for normoalbuminuria versus microalbuminuria, P < 0.001 for microalbuminuria versus macroalbuminuria). Urinary CTGF-N was lower (<30-fold) in macroalbuminuric subjects treated with ACE inhibitors (6.5 ×/÷ 1.7 ng/mg; P < 0.01 vs. untreated macroalbuminuria) compared with their untreated counterparts.

CONCLUSIONS—In this cross-sectional study, the magnitude of urinary CTGF-N excretion was related to the severity of diabetic nephropathy. In the context of its known profibrotic actions, these findings suggest that CTGF may contribute to the chronic tubulointerstitial fibrosis that accompanies proteinuric renal disease. Prospective and interventional studies will be needed to determine whether urinary CTGF-N may provide a reliable surrogate marker of renal injury and a meaningful indicator of response to therapy.
XENical in the Prevention of Diabetes in Obese Subjects (XENDOS) Study
Authors: Torgerson Jarl S. , Hauptman Jonathan , Boldrin Mark N. , Sjöström Lars
Published: March 2007

OBJECTIVE—It is well established that the risk of developing type 2 diabetes is closely linked to the presence and duration of overweight and obesity. A reduction in the incidence of type 2 diabetes with lifestyle changes has previously been demonstrated. We hypothesized that adding a weight-reducing agent to lifestyle changes may lead to an even greater decrease in body weight, and thus the incidence of type 2 diabetes, in obese patients.

RESEARCH DESIGN AND METHODS—In a 4-year, double-blind, prospective study, we randomized 3,305 patients to lifestyle changes plus either orlistat 120 mg or placebo, three times daily. Participants had a BMI ≥30 kg/m2 and normal (79%) or impaired (21%) glucose tolerance (IGT). Primary endpoints were time to onset of type 2 diabetes and change in body weight. Analyses were by intention to treat.

RESULTS—Of orlistat-treated patients, 52% completed treatment compared with 34% of placebo recipients (P < 0.0001). After 4 years’ treatment, the cumulative incidence of diabetes was 9.0% with placebo and 6.2% with orlistat, corresponding to a risk reduction of 37.3% (P = 0.0032). Exploratory analyses indicated that the preventive effect was explained by the difference in subjects with IGT. Mean weight loss after 4 years was significantly greater with orlistat (5.8 vs. 3.0 kg with placebo; P < 0.001) and similar between orlistat recipients with impaired (5.7 kg) or normal glucose tolerance (NGT) (5.8 kg) at baseline. A second analysis in which the baseline weights of subjects who dropped out of the study was carried forward also demonstrated greater weight loss in the orlistat group (3.6 vs. 1.4 kg; P < 0.001).

CONCLUSIONS—Compared with lifestyle changes alone, orlistat plus lifestyle changes resulted in a greater reduction in the incidence of type 2 diabetes over 4 years and produced greater weight loss in a clinically representative obese population. Difference in diabetes incidence was detectable only in the IGT subgroup; weight loss was similar in subjects with IGT and or NGT.
Glycemic Control From 1988 to 2000 Among U.S. Adults Diagnosed With Type 2 Diabetes
Authors: Koro Carol E. , Bowlin Steven J. , Bourgeois Nancy , Fedder Donald O.
Published: March 2007

OBJECTIVE—To describe the changes in demographics, antidiabetic treatment, and glycemic control among the prevalent U.S. adult diagnosed type 2 diabetes population between the National Health and Nutrition Examination Survey (NHANES) III (1988–1994) and the initial release of NHANES 1999–2000.

RESEARCH DESIGN AND METHODS—The study population was derived from NHANES III (n = 1,215) and NHANES 1999–2000 (n = 372) subjects who reported a diagnosis of type 2 diabetes with available data on diabetes medication and HbA1c. Four therapeutic regimens were defined: diet only, insulin only, oral antidiabetic drugs (OADs) only, or OADs plus insulin. Multiple logistic regression was used to examine changes in antidiabetic regimens and glycemic control rates over time, adjusted for demographic and clinical risk factors. The outcome measure for glycemic control was HbA1c. Glycemic control rates were defined as the proportion of type 2 diabetic patients with HbA1c level <7%.

RESULTS—Dietary treatment in individuals with diabetes decreased as the sole therapy from 27.4 to 20.2% between the surveys. Insulin use also decreased from 24.2 to 16.4%, while those on OADs only increased from 45.4 to 52.5%. Combination of OADs and insulin increased from 3.1 to 11.0%. Glycemic control rates declined from 44.5% in NHANES III (1988–1994) to 35.8% in NHANES 1999–2000.

CONCLUSIONS—Treatment regimens among U.S. adults diagnosed with type 2 diabetes have changed substantially over the past 10 years. However, a decrease in glycemic control rates was also observed during this time period. This trend may contribute to increased rates of macrovascular and microvascular diabetic complications, which may impact health care costs. Our data support the public health message of implementation of early, aggressive management of diabetes.
Postural Control Mechanisms During Quiet Standing in Patients With Diabetic Sensory Neuropathy
Authors: Lafond Danik , Corriveau Hélène , Prince Francois
Published: March 2007

OBJECTIVE—The objective of the present study was to compare postural mechanisms identified by using dual force platform in healthy elderly community-dwelling subjects and diabetic sensory neuropathy (DSN) patients under different visual conditions.

RESEARCH DESIGN AND METHODS—The presence and the severity of the sensory neuropathy was evaluated with a clinical scale. Postural mechanisms and motor strategies of the ankle and hip joints were quantified by testing subjects in quiet stance on a dual force platform under two visual conditions (eyes open and eyes closed). Root mean square (RMS) values of the center of pressure (COP) time-varying signals and normalized cross-correlation function were used to estimate the contribution and the interdependence of postural control mechanisms.

RESULTS—DSN patients show larger RMS values of the COPnet displacement in both anteroposterior and mediolateral (ML) directions. Motor strategies at the ankle joints are altered in DSN patients compared with healthy elderly subjects particularly in the ML direction.

CONCLUSIONS—This experiment is the first to highlight that even with vision, postural mechanisms at the ankle joints are impaired in DSN patients during quiet standing. Our results point out the importance of focusing on postural control instability in ML of DSN patients.
Improving Diabetes Care in Midwest Community Health Centers With the Health Disparities Collaborative
Authors: Chin Marshall H. , Cook Sandy , Drum Melinda L. , Jin Lei , Guillen Myriam , Humikowski Catherine A. , Koppert Julie , Harrison James F. , Lippold Susan , Schaefer Cynthia T.
Published: March 2007

OBJECTIVE—To evaluate the Diabetes Health Disparities Collaborative, an initiative by the Bureau of Primary Health Care to reduce health disparities and improve the quality of diabetes care in community health centers.

RESEARCH DESIGN AND METHODS—One year before- after trial. Beginning in 1998, 19 Midwestern health centers undertook a diabetes quality improvement initiative based on a model including rapid Plan-Do-Study-Act cycles from the continuous quality improvement field; a Chronic Care Model emphasizing patient self-management, delivery system redesign, decision support, clinical information systems, leadership, health system organization, and community outreach; and collaborative learning sessions. We reviewed charts of 969 random adults for American Diabetes Association standards, surveyed 79 diabetes quality improvement team members, and performed qualitative interviews.

RESULTS—The performance of several key processes of care assessed by chart review increased, including rates of HbA1c measurement (80–90%; adjusted odds ratio 2.1, 95% CI 1.6–2.8), eye examination referral (36–47%; 1.6, 1.1–2.3), foot examination (40–64%; 2.7, 1.8–4.1), and lipid assessment (55–66%; 1.6, 1.1–2.3). Mean value of HbA1c tended to improve (8.5–8.3%; difference −0.2, 95% CI −0.4 to 0.03). Over 90% of survey respondents stated that the Diabetes Collaborative was worth the effort and was successful. Major challenges included needing more time and resources, initial difficulty developing computerized patient registries, team and staff turnover, and occasional need for more support by senior management.

CONCLUSIONS—The Health Disparities Collaborative improved diabetes care in health centers in 1 year.
A Controlled Trial of Population Management
Authors: Grant Richard W. , Cagliero Enrico , Sullivan Christine M. , Dubey Anil K. , Estey Greg A. , Weil Eric M. , Gesmundo Joseph , Nathan David M. , Singer Daniel E. , Chueh Henry C. , Meigs James B.
Published: March 2007

OBJECTIVE—Population-level strategies to organize and deliver care may improve diabetes management. We conducted a multiclinic controlled trial of population management in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS—We created diabetic patient registries (n = 3,079) for four primary care clinics within a single academic health center. In the intervention clinic (n = 898), a nurse practitioner used novel clinical software (PopMan) to identify patients on a weekly basis with outlying values for visit and testing intervals and last measured levels of HbA1c, LDL cholesterol, and blood pressure. For these patients, the nurse practitioner e-mailed a concise patient-specific summary of evidence-based management suggestions directly to primary care providers (PCPs). Population changes in risk factor testing, medication prescription, and risk factor levels from baseline (1 January 2000 to 31 August 2001) to follow-up (1 December 2001 to 31 July 2003) were compared with the three usual-care control clinics (n = 2,181).

RESULTS—Patients had a mean age of 65 years, were mostly white (81%), and the majority were insured by Medicare/Medicaid (62%). From baseline to follow-up, the increase in proportion of patients tested for HbA1c (P = 0.004) and LDL cholesterol (P < 0.001) was greater in the intervention than control sites. Improvements in diabetes-related medication prescription and levels of HbA1c, LDL cholesterol, and blood pressure in the intervention clinic were balanced by similar improvements in the control sites.

CONCLUSIONS—Population-level clinical registries combined with summarized recommendations to PCPs had a modest effect on management. The intervention was limited by good overall quality of care at baseline and temporal improvements in all control clinics. It is unknown whether this intervention would have had greater impact in clinical settings with lower overall quality. Further research into more effective methods of translating population registry information into action is required.
A Population-Based Study of Diabetes and Its Characteristics During the Fasting Month of Ramadan in 13 Countries
Authors: Salti Ibrahim , Bénard Eric , Detournay Bruno , Bianchi-Biscay Monique , Le Brigand Corinne , Voinet Céline , Jabbar Abdul ,   on behalf of the EPIDIAR Study Group
Published: March 2007

OBJECTIVE—The aim of this study was to assess the characteristics and care of patients with diabetes in countries with a sizable Muslim population and to study diabetes features during Ramadan and the effect of fasting.

RESEARCH DESIGN AND METHODS—This was a population-based, retrospective, transversal survey conducted in 13 countries. A total of 12,914 patients with diabetes were recruited using a stratified sampling method, and 12,243 were considered for the analysis.

RESULTS—Investigators recruited 1,070 (8.7%) patients with type 1 diabetes and 11,173 (91.3%) patients with type 2 diabetes. During Ramadan, 42.8% of patients with type 1 diabetes and 78.7% with type 2 diabetes fasted for at least 15 days. Less than 50% of the whole population changed their treatment dose (approximately one-fourth of patients treated with oral antidiabetic drugs [OADs] and one-third of patients using insulin). Severe hypoglycemic episodes were significantly more frequent during Ramadan compared with other months (type 1 diabetes, 0.14 vs. 0.03 episode/month, P = 0.0174; type 2 diabetes, 0.03 vs. 0.004 episode/month, P < 0.0001). Severe hypoglycemia was more frequent in subjects who changed their dose of OADs or insulin or modified their level of physical activity.

CONCLUSIONS—The large proportion of both type 1 and type 2 diabetic subjects who fast during Ramadan represent a challenge to their physicians. There is a need to provide more intensive education before fasting, to disseminate guidelines, and to propose further studies assessing the impact of fasting on morbidity and mortality.
The Metabolic Syndrome Defined by Factor Analysis and Incident Type 2 Diabetes in a Chinese Population With High Postprandial Glucose
Authors: Wang Jian-jun , Qiao Qing , Miettinen Maija E. , Lappalainen Jani , Hu Gang , Tuomilehto Jaakko
Published: March 2007

OBJECTIVE—The aim of this study was to examine how the major components of the metabolic syndrome relate to each other and to the development of diabetes using factor analysis.

RESEARCH DESIGN AND METHODS—The screening survey for type 2 diabetes was conducted in 1994, and a follow-up study of nondiabetic individuals at baseline was carried out in 1999 in the Beijing area. Among 934 nondiabetic and 305 diabetic subjects at baseline, factor analysis was performed using the principle components analysis with varimax orthogonal rotation of continuously distributed variables considered to represent the components of the metabolic syndrome. Fasting insulin was used as a marker for insulin resistance. Of the 559 subjects without diabetes at baseline, 129 developed diabetes during the 5-year follow-up. Factors identified at baseline were used as independent variables in univariate and multivariate logistic regression models to determine risk factor clusters predicting the development of diabetes.

RESULTS—Four factors were identified in nondiabetic and diabetic subjects. Fasting insulin levels, BMI, and waist-to-hip ratio were associated with one factor. Systolic and diastolic blood pressures were associated with the second factor. Two-hour postload plasma glucose (2-h PG) and serum insulin and fasting plasma glucose were associated with the third factor. Serum total cholesterol and triglycerides were associated with the fourth factor. The first and the third factors predicted the development of diabetes. In diabetic patients at baseline, the combination of systolic and diastolic blood pressure was the most important factor, and urinary albumin excretion rate clustered with fasting and 2-h PG levels.

CONCLUSIONS—Insulin resistance alone does not underlie all features of the metabolic syndrome. Different physiological processes associated with various components of the metabolic syndrome contain unique information about diabetes risk. Microalbunuria is more likely to be a complication of type 2 diabetes or hypertension than a marker for the metabolic syndrome.
Decreased Plasma Lipoprotein Lipase in Hypoadiponectinemia
Authors: von Eynatten Maximilian , Schneider Jochen G. , Humpert Per M. , Rudofsky Gottfried , Schmidt Nikolaus , Barosch Patrizia , Hamann Andreas , Morcos Michael , Kreuzer Joerg , Bierhaus Angelika , Nawroth Peter P. , Dugi Klaus A.
Published: March 2007

OBJECTIVE—Adiponectin is a plasma protein expressed in adipose tissue. Hypoadiponectinemia is associated with low HDL cholesterol and high plasma triglycerides, which also characterize lipoprotein lipase (LPL) deficiency syndromes. Recently, dramatically increased LPL activity was reported in mice overexpressing adiponectin. We therefore speculated that adiponectin may directly affect LPL in humans.

RESEARCH DESIGN AND METHODS—We measured plasma adiponectin and postheparin LPL in 206 nondiabetic men and in a second group of 110 patients with type 2 diabetes. Parameters were correlated with markers of systemic inflammation (C-reactive protein [CRP]) and insulin resistance (homeostatis model assessment of insulin resistance [HOMA-IR]).

RESULTS—Nondiabetic subjects with decreased plasma adiponectin had lower LPL activity (r = 0.42, P < 0.0001). This association of plasma adiponectin with LPL activity was confirmed in the second group of patients with type 2 diabetes (r = 0.37, P < 0.0001). Multivariate analysis revealed that adiponectin was the strongest factor influencing LPL activity, accounting for 23% of the variation in LPL activity in nondiabetic subjects and for 26% of the variation in LPL activity in type 2 diabetic patients. These associations were independent of plasma CRP and HOMA-IR.

CONCLUSIONS—These results demonstrate an association of decreased postheparin LPL activity with low plasma adiponectin that is independent of systemic inflammation and insulin resistance. Therefore, LPL may represent a link between low adiponectin levels and dyslipidemia in both nondiabetic individuals and patients with type 2 diabetes.
Association Between Inflammation and Insulin Resistance in U.S. Nondiabetic Adults
Authors: Chen Jing , Wildman Rachel P. , Hamm L. Lee , Muntner Paul , Reynolds Kristi , Whelton Paul K. , He Jiang
Published: March 2007

Clinical and epidemiological data indicate that inflammation may be associated with insulin resistance. We examined the association between inflammatory markers, such as ferritin, uric acid, white cell counts, fibrinogen, and C-reactive protein, and insulin resistance among 5,959 adults, aged ≥20 years and without diabetes (fasting glucose <126 mg/dl and not taking diabetes medication), who participated in the Third National Health and Nutrition Examination Survey. Insulin resistance was calculated using the homeostasis model assessment (HOMA). Levels of ferritin, uric acid, white cell counts, fibrinogen, and C-reactive protein were significantly higher in individuals with a higher HOMA of insulin resistance (HOMA-IR). After adjustment for age, sex, race, education, physical inactivity, current and former smoking, alcohol intake, use of nonsteroidal anti-inflammatory drugs, systolic blood pressure, BMI, waist circumference, serum total cholesterol, and triglycerides, a 1-SD higher ferritin (126.1 ng/ml), uric acid (1.4 mg/dl), white blood cell count (2.2 × 109/l), and fibrinogen (80.6 mg/dl) was associated with a 0.10 (95% CI 0.03–0.17, P = 0.004), 0.16 (0.08–0.24, P < 0.001), 0.16 (0.09–0.22, P < 0.001), and 0.12 (0.05–0.18, P = 0.001) higher HOMA-IR, respectively. Clinically elevated C-reactive protein (≥1.0 mg/dl) was associated with a 0.63 (0.23–1.04, P = 0.003) higher HOMA-IR. These findings indicate that elevated levels of inflammatory markers are positively and independently associated with insulin resistance. Further studies should examine the potential causal effect of inflammation on insulin resistance.