bluuebunny/crossref_metadata_2025 huggingface dataset:
The Incidence of Congestive Heart Failure in Type 2 Diabetes
Authors: Nichols Gregory A. , Gullion Christina M. , Koro Carol E. , Ephross Sara A. , Brown Jonathan B.
Published: March 2007

OBJECTIVE—The aims of this study were to update previous estimates of the congestive heart failure (CHF) incidence rate in patients with type 2 diabetes, compare it with an age- and sex-matched nondiabetic group, and describe risk factors for developing CHF in diabetic patients over 6 years of follow-up.

RESEARCH DESIGN AND METHODS—We performed a retrospective cohort study of 8,231 patients with type 2 diabetes and 8,845 nondiabetic patients of similar age and sex who did not have CHF as of 1 January 1997, following them for up to 72 months to estimate the CHF incidence rate. In the diabetic cohort, we constructed a Cox regression model to identify risk factors for CHF development.

RESULTS—Patients with diabetes were much more likely to develop CHF than patients without diabetes (incidence rate 30.9 vs. 12.4 cases per 1,000 person-years, rate ratio 2.5, 95% CI 2.3–2.7). The difference in CHF development rates between persons with and without diabetes was much greater in younger age-groups. In addition to age and ischemic heart disease, poorer glycemic control (hazard ratio 1.32 per percentage point of HbA1c) and greater BMI (1.12 per 2.5 units of BMI) were important predictors of CHF development.

CONCLUSIONS—The CHF incidence rate in type 2 diabetes may be much greater than previously believed. Our multivariate results emphasize the importance of controlling modifiable risk factors for CHF, namely hyperglycemia, elevated blood pressure, and obesity. Younger patients may benefit most from risk factor modification.
Are We Underestimating Diabetes-Related Lower-Extremity Amputation Rates?
Authors: Rayman Gerry , Krishnan Singhan T.M. , Baker Neil R. , Wareham Alison M. , Rayman Anne
Published: March 2007

OBJECTIVE—The objective of this study was to accurately determine the incidence of lower-extremity amputation using prospective data collection and to compare the results with those obtained by retrospective methods.

RESEARCH DESIGN AND METHODS—The study was carried out over a 3-year period in a large district general hospital covering a clearly defined and relatively static population. All diabetic inpatients with foot problems were identified and followed-up until discharge or death. The demographic and admission details, medical history, investigations, procedures, and history and etiology of the foot lesion were collected twice weekly by a specialist nurse and podiatrist from all relevant wards. Thus, all subjects who underwent amputation could be identified. For comparison, retrospective data were collected from the hospital coding activities database, operating theater log books, anesthetic database, and limb-fitting records.

RESULTS—The total population of the region in 2000 was 337,859, of which 9,183 were known to have diabetes. The total number of amputations during the 3-year survey period was 79, of which 45 were major and 34 minor. In our local population, the mean incidence during the survey period (1997–2000) equates to 7.8/100,000 general population and 2.85/1,000 diabetic population for all amputations, 4.5/100,000 general population and 1.62/1,000 diabetic population for major amputations, and 3.3/100,000 general population and 1.23/1,000 diabetic population for minor amputations. The prospective survey detected all lower-extremity amputations identified by the various retrospective methods; however, for the reverse, this was not the case. All of the retrospective methods, including the most commonly used (ICD-9 and OPCS-4 coding), failed to detect all of the cases revealed by the prospective survey (error rate ranging from 4.2 to 90.6%), and between 4.5 and 17.4% of amputations were misclassified.

CONCLUSIONS—This study demonstrates the advantages of prospective data collection as a means of determining the incidence of lower-extremity amputations and highlights the limitations of retrospective data collection methods, which underestimate the incidence. In particular, the operating theater records, which have been the gold standard for many surveys, were found to be unreliable. Moreover, we have shown a 47% reduction in the major amputations during the survey period. Thus, we recommend that a prospective audit be incorporated into the activities of the specialist foot care team as a means of assessing and improving clinical care.
Distinct Diagnostic Criteria of Fulminant Type 1 Diabetes Based on Serum C-Peptide Response and HbA1c Levels at Onset
Authors: Tanaka Shoichiro , Endo Toyoshi , Aida Kaoru , Shimura Hiroki , Yokomori Norihiko , Kaneshige Masahiro , Furuya Fumihiko , Amemiya Shin , Mochizuki Mie , Nakanishi Koji , Kobayashi Tetsuro
Published: March 2007

OBJECTIVE—Diagnostic criteria in fulminant type 1 diabetes, a novel subtype of type 1 diabetes, remain unclear.

RESEARCH DESIGN AND METHODS—We analyzed basal and longitudinal changes of serum C-peptide levels during a 75-g oral glucose tolerance test (OGTT) in 125 consecutively recruited patients with type 1 diabetes including fulminant type 1 diabetes (n = 25) and acute-onset type 1 diabetes (n = 100). Discriminating criteria of fulminant type 1 diabetes were examined using receiver-operating characteristic curve analysis and multiple logistic regression analysis.

RESULTS—The integrated values of serum C-peptide response during OGTT (ΣC-peptide) in fulminant type 1 diabetes at onset, 1 year, and 2 years after onset were markedly lower than those in acute-onset type 1 diabetes. None of the patients with fulminant type 1 diabetes had improvement of C-peptide response to OGTT. Fasting C-peptide values at onset in fulminant type 1 diabetes were significantly lower than those in acute-onset type 1 diabetes. We established diagnostic criteria of serum C-peptide and HbA1c levels at onset that discriminate fulminant type 1 diabetes from acute-onset type 1 diabetes with high sensitivity and specificity: a criterion in which the levels of both the fasting C-peptide is ≤0.033 nmol/l and HbA1c is ≤8.0% or a criterion in which the levels of both the ΣC-peptide is ≤0.540 nmol/l and HbA1c is ≤8.0%.

CONCLUSIONS—Fulminant type 1 diabetes has extremely low β-cell function at onset that rarely recovers after onset. Sensitive and specific diagnostic criteria were established for detection of fulminant type 1 diabetes based on serum C-peptide and HbA1c levels at onset.
Detection of Silent Myocardial Ischemia in Asymptomatic Diabetic Subjects
Authors: Wackers Frans J.Th. , Young Lawrence H. , Inzucchi Silvio E. , Chyun Deborah A. , Davey Janice A. , Barrett Eugene J. , Taillefer Raymond , Wittlin Steven D. , Heller Gary V. , Filipchuk Neil , Engel Samuel , Ratner Robert E. , Iskandrian Ami E. ,   for the Detection of Ischemia in Asymptomatic Diabetics (DIAD) Investigators
Published: March 2007

OBJECTIVE—To assess the prevalence and clinical predictors of silent myocardial ischemia in asymptomatic patients with type 2 diabetes and to test the effectiveness of current American Diabetes Association screening guidelines.

RESEARCH DESIGN AND METHODS—In the Detection of Ischemia in Asymptomatic Diabetics (DIAD) study, 1,123 patients with type 2 diabetes, aged 50–75 years, with no known or suspected coronary artery disease, were randomly assigned to either stress testing and 5-year clinical follow-up or to follow-up only. The prevalence of ischemia in 522 patients randomized to stress testing was assessed by adenosine technetium-99m sestamibi single-photon emission–computed tomography myocardial perfusion imaging.

RESULTS—A total of 113 patients (22%) had silent ischemia, including 83 with regional myocardial perfusion abnormalities and 30 with normal perfusion but other abnormalities (i.e., adenosine-induced ST-segment depression, ventricular dilation, or rest ventricular dysfunction). Moderate or large perfusion defects were present in 33 patients. The strongest predictors for abnormal tests were abnormal Valsalva (odds ratio [OR] 5.6), male sex (2.5), and diabetes duration (5.2). Other traditional cardiac risk factors or inflammatory and prothrombotic markers were not predictive. Ischemic adenosine-induced ST-segment depression with normal perfusion (n = 21) was associated with women (OR 3.4). Selecting only patients who met American Diabetes Association guidelines would have failed to identify 41% of patients with silent ischemia.

CONCLUSIONS—Silent myocardial ischemia occurs in greater than one in five asymptomatic patients with type 2 diabetes. Traditional and emerging cardiac risk factors were not associated with abnormal stress tests, although cardiac autonomic dysfunction was a strong predictor of ischemia.
Does the Aspartic Acid to Asparagine Substitution at Position 76 in the Pancreas Duodenum Homeobox Gene (PDX1) Cause Late-Onset Type 2 Diabetes?
Authors: Elbein Steven C. , Karim Mohammad A.
Published: March 2007

OBJECTIVE—Considerable data support an inherited defect in insulin secretion as one component of type 2 diabetes. Coding variants of the pancreas duodenum homeobox gene (PDX1) were proposed to predispose late-onset type 2 diabetes and to decrease transactivation in vitro. We tested the hypothesis that the Asp76Asn (D76N) variant that was identified in several populations predisposed type 2 diabetes and reduced insulin secretion.

RESEARCH DESIGN AND METHODS—We performed a case-control study in 191 control subjects and 190 individuals with type 2 diabetes, all of European descent, then characterized the D76N variant in 704 members of 68 families. We compared the phenotypic characteristics of those with and without the variant by diagnostic status and determined the insulin secretory response to intravenous glucose and tolbutamide among nondiabetic family members.

RESULTS—D76N was not associated with type 2 diabetes, either in our population or when all reported studies in Caucasians were combined. D76N did not segregate with diabetes among the families examined. Among D76N carriers, nondiabetic individuals had a lower waist-to-hip ratio and a trend to lower BMI than their diabetic counterparts. Diabetic carriers of D76N were significantly leaner by BMI (P = 0.012) and tended to be younger than diabetic individuals with the D/D genotype. However, insulin secretion in response to oral and intravenous glucose challenge and to intravenous tolbutamide was not reduced in D76N carriers.

CONCLUSIONS—The D76N variant of PDX1 does not significantly alter insulin secretion or act as a high-risk susceptibility allele for late-onset type 2 diabetes as proposed previously, although we cannot exclude a minor role in increasing risk of diabetes.
The +276 G/T Single Nucleotide Polymorphism of the Adiponectin Gene Is Associated With Coronary Artery Disease in Type 2 Diabetic Patients
Authors: Bacci Simonetta , Menzaghi Claudia , Ercolino Tonino , Ma Xiaowei , Rauseo Anna , Salvemini Lucia , Vigna Carlo , Fanelli Raffaele , Di Mario Umberto , Doria Alessandro , Trischitta Vincenzo
Published: March 2007

OBJECTIVE—Two single nucleotide polymorphisms (SNPs) at the adiponectin locus (+45T>G and +276G>T) have been associated with low circulating adiponectin levels, insulin resistance, and type 2 diabetes. We investigated whether these genetic markers are determinants of coronary artery disease (CAD) in type 2 diabetic patients.

RESEARCH DESIGN AND METHODS—A total of 376 consecutive type 2 diabetic patients were studied: 142 case subjects with coronary stenosis >50% or previous myocardial infarction and 234 control subjects with no symptoms, no electrocardiogram (ECG) signs of myocardial ischemia, and a normal ECG stress test (n = 189) and/or (n = 45) with coronary stenosis ≤50%.

RESULTS—No association with CAD was observed for the +45 SNP (P = 0.48). By contrast, a significant association was observed for the +276 SNP, with T/T homozygotes having a lower risk of CAD than carriers of other genotypes (adjusted odds ratio [OR] 0.13 [95% CI 0.037–0.46], P = 0.002). A similarly protective effect of the +276 T/T genotype was observed in 110 case and 45 control subjects for whom the CAD status had been determined by angiography (0.04 [0.006–0.30], P = 0.002).  Serum adiponectin, although clearly related to several features of the proatherogenic/insulin-resistant phenotype, was not different between control subjects and CAD patients (26 ± 17 vs. 25 ± 13 μg/ml).

CONCLUSIONS—In conclusion, the +276 G>T polymorphism is a determinant of CAD risk in type 2 diabetic patients. This marker may assist in the identification of diabetic individuals at especially high risk of CAD, so that preventive programs can be targeted at these subjects.
Features of the Metabolic Syndrome Are Associated With Objectively Measured Physical Activity and Fitness in Danish Children
Authors: Brage Søren , Wedderkopp Niels , Ekelund Ulf , Franks Paul W. , Wareham Nicholas J. , Andersen Lars Bo , Froberg Karsten
Published: March 2007

OBJECTIVE—Features of the metabolic syndrome are becoming increasingly evident in children. Decreased physical activity is likely to be an important etiological factor, as shown previously for subjective measures of physical activity in selected groups. The purpose of this study was to examine the relationship between the metabolic syndrome and objectively measured physical activity and whether fitness modified this relationship.

RESEARCH DESIGN AND METHODS—A total of 589 Danish children (310 girls, 279 boys, mean [±SD] age 9.6 ± 0.44 years, mean weight 33.6 ± 6.4 kg, mean height 1.39 ± 0.06 m) were randomly selected. Physical activity was measured with the uni-axial Computer Science & Applications accelerometer (MTI actigraph) worn at the hip for at least 3 days (≥10 h/day) and fitness with a maximal bike test. As outcomes, we measured sitting systolic and diastolic blood pressure, degree of adiposity (sum of four skinfolds), and, finally, insulin, glucose, triglicerides, and HDL cholesterol in fasting blood samples. The outcome variables were statistically normalized and expressed as the number of SDs from the mean. (i.e., Z scores). A metabolic syndrome risk score was computed as the mean of these Z scores. Multiple linear regression was used to test the association between physical activity and metabolic risk, adjusted primarily for age, sex, sexual maturation, ethnicity, parental smoking, socioeconomic factors, and the Computer Science & Applications unit, as well as for fitness. Robust SEs were computed by clustering on school.

RESULTS—All children were in the nondiabetic range of fasting glucose. Metabolic risk was inversely related to physical activity (P = 0.008). The relationship was weakened after adjustment for fitness, but there was a significantly positive interaction between physical activity and fitness.

CONCLUSIONS—Physical activity is inversely associated with metabolic risk, independently of potential confounders. The interaction between physical activity and fitness suggests that the potential beneficial effect of activity may be greatest in children with lower cardiorespiratory fitness.
Contribution of Insulin-Stimulated Glucose Uptake and Basal Hepatic Insulin Sensitivity to Surrogate Measures of Insulin Sensitivity
Authors: Tripathy Devjit , Almgren Peter , Tuomi Tiinamaija , Groop Leif
Published: March 2007

OBJECTIVE—The goal of this study was to evaluate the performance of surrogate measures of insulin sensitivity and insulin secretion.

RESEARCH DESIGN AND METHODS—The homeostasis model assessment (HOMA) of insulin resistance (IR) and the insulin sensitivity index (Si) from oral glucose tolerance test (OGTT) were compared with the M value from a hyperinsulinemic-euglycemic clamp in 467 subjects with various degrees of glucose tolerance. Endogenous glucose production (EGP) and hepatic insulin sensitivity were determined in a subset (n = 143). Insulin secretion was estimated as the HOMA β-cell index and as the insulinogenic index from the first 30 min of the OGTT (I/G30) and compared with the first-phase insulin response (FPIR) to an intravenous glucose tolerance test (n = 218).

RESULTS—The M value correlated with the HOMA-IR (r = −0.591, P < 0.0001) and the Si (r = 0.533, P < 0.0001) indexes in the total study group. HOMA-IR correlated with basal EGP in the total study group (r = 0.378, P < 0.0005) and in subjects with diabetes (r = 0.330, P = 0.01). However, neither HOMA-IR nor Si correlated significantly with the M value in subjects with impaired fasting glucose (IFG) (r = −0.108, P = 0.5; r = 0.01, P = 0.9) or IFG/impaired glucose tolerance (IGT) (r = −0.167, P = 0.4; r = 0.09, P = 0.6). The HOMA-IR correlated with hepatic insulin sensitivity in the whole study group (r = −0.395, P < 0.005) as well as in the IFG/IGT subgroup (r = −0.634, P = 0.002) and in the diabetic subgroup (r = −0.348, P = 0.008). In subjects with IFG/IGT, hepatic insulin sensitivity was the most important determinant of HOMA-IR, explaining 40% of its variation. The HOMA β-cell index showed a weak correlation with FPIR in the whole study group (r = 0.294, P = 0.001) but not in the subgroups. In contrast, the I/G30 correlated with FPIR in the whole study group (r = 0.472, P < 0.0005) and in the IFG/IGT subgroup (r = 0.493, P < 0.005).

CONCLUSIONS—HOMA-IR is dependent upon both peripheral and hepatic insulin sensitivity, the contribution of which differs between subjects with normal and elevated fasting glucose concentrations. These discrepancies develop as a consequence of a nonparallel deterioration of the variables included in the equations with worsening of glucose tolerance.
Lower Toenail Chromium in Men With Diabetes and Cardiovascular Disease Compared With Healthy Men
Authors: Rajpathak Swapnil , Rimm Eric B. , Li Tricia , Morris J. Steven , Stampfer Meir J. , Willett Walter C. , Hu Frank B.
Published: March 2007

OBJECTIVE—Chromium may improve insulin sensitivity, which can modify the risk of diabetes and cardiovascular disease (CVD). Therefore, we evaluated the association between toenail chromium and CVD in diabetic men.

RESEARCH DESIGN AND METHODS—We performed cross-sectional and nested case-control analyses among men aged 40–75 years within the Health Professionals Follow-up Study. The cross-sectional analysis compared men with diabetes only (n = 688), diabetes with prevalent CVD (n = 198), and healthy control subjects (n = 361). The nested case-control study included 202 men with baseline diabetes who developed incident CVD and 361 matched control subjects.

RESULTS—Mean toenail chromium (μg/g) was 0.71 in healthy control subjects, 0.61 in diabetes-only subjects, and 0.52 in diabetic subjects with prevalent CVD (P for trend = 0.003). In the cross-sectional analysis, the multivariate odds ratio (OR) between extreme quartiles was 0.74 (95% CI 0.49–1.11; P for trend = 0.18), comparing diabetes only with healthy control subjects. A similar comparison between diabetic subjects with prevalent CVD and healthy control subjects yielded an OR of 0.45 (0.24–0.84; P for trend = 0.003). In the nested case-control study, comparing diabetic men with incident CVD with healthy control subjects, the multivariate OR was 0.65 (0.36–1.17; P for trend = 0.16) between extreme quartiles. When we combined prevalent and incident CVD cases among diabetic men and compared them with healthy control subjects, the OR was 0.62 (0.39–1.01; P for trend = 0.02) between extreme quartiles.

CONCLUSIONS—Our results suggest that diabetic men with CVD have lower toenail chromium than healthy control subjects. However, this study could not distinguish between the effects of chromium on diabetes and those on CVD. Long-term clinical trials are needed to determine whether chromium supplementation is beneficial for preventing CVD among diabetic patients.
Metabolic Syndrome in Normal-Weight Americans
Authors: St-Onge Marie-Pierre , Janssen Ian , Heymsfield Steven B.
Published: March 2007

OBJECTIVE—To determine the prevalence rates and likelihood of the metabolic syndrome and its individual components in normal-weight and slightly overweight individuals (BMI 18.5–26.9 kg/m2).

RESEARCH DESIGN AND METHODS—There were a total of 7,602 adult participants of the Third National Health and Nutrition Examination Survey, a nationally representative cross-sectional survey. Prevalence and odds ratios (ORs) of the metabolic syndrome, defined according to National Cholesterol Education Program Adult Treatment Panel III criteria, were computed according to 2.0- to 2.5-unit increments in BMI.

RESULTS—Depending on ethnicity and sex, the prevalence of the metabolic syndrome increased in a graded fashion from 0.9–3.0% at BMI 18.5–20.9 kg/m2 to 9.6–22.5% at BMI 25.0–26.9 kg/m2. Compared with men with BMI 18.5–20.9 kg/m2, the odds for the metabolic syndrome were 4.13 (95% CI 1.57–10.87) for men with BMI 21–22.9 kg/m2, 5.35 (2.41–11.86) for men with BMI 23–24.9 kg/m2, and 9.08 (4.23–19.52) for men with BMI 25–26.9 kg/m2 after controlling for age, ethnicity, education, income, physical activity, smoking status, and alcohol and total fat, saturated fat, carbohydrate, and fiber intakes. The corresponding ORs in women were 4.34 (2.08–9.07), 7.77 (3.95–15.26), and 17.34 (9.29–32.38).

CONCLUSIONS—Individuals in the upper normal-weight and slightly overweight BMI range have a relatively high prevalence and are at increased risk of having the metabolic syndrome. Therefore, screening in individuals with normal or slightly elevated BMI is important in the prevention of diabetes and cardiovascular disease.
Development of Evidence-Based Clinical Practice Guidelines for Diabetes
Authors: Pogach Leonard M. , Brietzke Stephen A. , Cowan, Jr. Claude L. , Conlin Paul , Walder Debby J. , Sawin Clark T. ,   for the VA/DoD Diabetes Guideline Development Group*
Published: March 2007

OBJECTIVE—To describe the Veterans Affairs (VA)/Department of Defense (DoD) Clinical Practice Guidelines for diabetes and contrast selected recommendations with those of the American Diabetes Association (ADA).

RESEARCH DESIGN AND METHODS—We summarize the general structure of the VA/DoD Guidelines and describe the rationale for recommendations issued in 2003 for glycemic control, management of hypertension, and retinopathy screening. We compare the synthesis of evidence and resulting recommendations for these content areas with the 2004 American Diabetes Association Clinical Practice Recommendations.

RESULTS—The VA/DoD Guidelines and the ADA Clinical Practice Recommendations reported similar strength of evidence findings by content area, but clinical recommendations varied. The VA/DoD Guidelines and practice recommendations emphasize the use of data on absolute risk reduction from available published randomized clinical trials rather than relative risk reduction from observational analyses. The VA/DoD Guidelines employ an algorithm-based methodology to guide clinicians through a risk-stratified approach to managing individual patients rather than promoting a single standard for most or all patients without explicit consideration of competing comorbidities.

CONCLUSIONS—The VA/DoD Guidelines are intended to guide diabetes care by providing Internet-ready, evidence-based annotations in algorithmic form to help clinicians set and revise individual treatment goals for their patients.
Plasma Concentration of IGF-I Is Independently Associated With Insulin Sensitivity in Subjects With Different Degrees of Glucose Tolerance
Authors: Sesti Giorgio , Sciacqua Angela , Cardellini Marina , Marini Maria Adelaide , Maio Raffaele , Vatrano Marco , Succurro Elena , Lauro Renato , Federici Massimo , Perticone Francesco
Published: March 2007

OBJECTIVE—We studied the relationships between plasma IGF-I concentrations and insulin sensitivity in subjects with various degrees of glucose tolerance.

RESEARCH DESIGN AND METHODS—A total of 357 nondiabetic subjects, 54 subjects with impaired glucose tolerance and 98 newly diagnosed type 2 diabetic subjects, were consecutively recruited, and anthropometric and biochemical characteristics were collected.

RESULTS—IGF-I concentrations were negatively correlated with age, BMI, waist-to-hip ratio, triglyceride levels, and systolic and diastolic blood pressure. IGF-I concentrations were positively correlated with HDL cholesterol and homeostasis model assessment of insulin sensitivity (HOMA-S). The correlations remained significant after adjusting for sex, age, and BMI. Correlations for HOMA-S with these metabolic and anthropometric variables were of a similar degree and direction to those for IGF-I concentrations. Stepwise linear regression analysis in a model, which included well-known modulators of insulin sensitivity such as sex, age, BMI, glucose tolerance status, family history of diabetes, waist-to-hip ratio, systolic and diastolic blood pressure, HDL cholesterol, and triglyceride levels, revealed that IGF-I concentrations were independently associated with insulin sensitivity accounting for 10.8% of its variation (P < 0.0001). IGF-I concentrations were significantly lower in subjects with World Health Organization (WHO)-defined metabolic syndrome compared with subjects without metabolic syndrome (P < 0.0001). Logistic regression analysis showed that each unit increase in log-transformed IGF-I concentrations was associated with a 90.5% reduction in the risk of WHO-defined metabolic syndrome.

CONCLUSIONS—These data indicate that IGF-I has the characteristics to be a marker for the insulin resistance syndrome. This suggests that low IGF-I levels may be a useful marker for identifying subjects at risk for cardiovascular disease.
Metabolic Syndrome Among HIV-Infected Patients
Authors: Jericó Carlos , Knobel Hernando , Montero Milagro , Ordoñez-Llanos Jordi , Guelar Ana , Gimeno Juan L. , Saballs Pere , López-Colomés Jose L. , Pedro-Botet Juan
Published: March 2007

OBJECTIVE—To assess the prevalence in HIV-infected patients of the metabolic syndrome as defined by the National Cholesterol Education Program, i.e., three or more of the following components: abdominal obesity, hypertriglyceridemia, low HDL cholesterol, high blood pressure, and high fasting glucose.

RESEARCH DESIGN AND METHODS—In this cross-sectional study, 710 HIV-infected patients managed at the outpatient clinic of a tertiary hospital during 2003 completed the study protocol consisting of a medical examination and laboratory analysis after a 12-h overnight fast.

RESULTS—Metabolic syndrome prevalence was 17% and increased from 5.1% among HIV-infected patients under age 30 years to 27.0% for those aged 50–59 years. Age (per 10-year increment) (odds ratio [OR] 1.41 [95% CI 1.12–1.77]), BMI (1.27 [1.19–1.36]), past and present protease inhibitor exposure (2.96 [1.03–3.55] and 4.18 [1.4–12.5], respectively) were independently associated with the metabolic syndrome on logistic regression analysis. Furthermore, only stavudine (d4T) (1.74 [1.01–2.98]) and lopinavir/ritonavir (2.46 [1.28–4.71]) were associated with the metabolic syndrome after adjustment for age and BMI.

CONCLUSIONS—The prevalence of metabolic syndrome among these HIV-infected patients is similar to that previously reported in uninfected individuals. Of specific concern is the association of protease inhibitor exposure with the metabolic syndrome and, more specifically, with exposure to stavudine and lopinavir/ritonavir when individual antiretroviral drugs were analyzed.
Diabetic Nephropathy: Diagnosis, Prevention, and Treatment
Authors: Gross Jorge L. , de Azevedo Mirela J. , Silveiro Sandra P. , Canani Luís Henrique , Caramori Maria Luiza , Zelmanovitz Themis
Published: March 2007

Diabetic nephropathy is the leading cause of kidney disease in patients starting renal replacement therapy and affects ∼40% of type 1 and type 2 diabetic patients. It increases the risk of death, mainly from cardiovascular causes, and is defined by increased urinary albumin excretion (UAE) in the absence of other renal diseases. Diabetic nephropathy is categorized into stages: microalbuminuria (UAE >20 μg/min and ≤199 μg/min) and macroalbuminuria (UAE ≥200 μg/min). Hyperglycemia, increased blood pressure levels, and genetic predisposition are the main risk factors for the development of diabetic nephropathy. Elevated serum lipids, smoking habits, and the amount and origin of dietary protein also seem to play a role as risk factors. Screening for microalbuminuria should be performed yearly, starting 5 years after diagnosis in type 1 diabetes or earlier in the presence of puberty or poor metabolic control. In patients with type 2 diabetes, screening should be performed at diagnosis and yearly thereafter. Patients with micro- and macroalbuminuria should undergo an evaluation regarding the presence of comorbid associations, especially retinopathy and macrovascular disease. Achieving the best metabolic control (A1c <7%), treating hypertension (<130/80 mmHg or <125/75 mmHg if proteinuria >1.0 g/24 h and increased serum creatinine), using drugs with blockade effect on the renin-angiotensin-aldosterone system, and treating dyslipidemia (LDL cholesterol <100 mg/dl) are effective strategies for preventing the development of microalbuminuria, in delaying the progression to more advanced stages of nephropathy and in reducing cardiovascular mortality in patients with type 1 and type 2 diabetes.
Periodontal Disease and Mortality in Type 2 Diabetes
Authors: Saremi Aramesh , Nelson Robert G. , Tulloch-Reid Marshall , Hanson Robert L. , Sievers Maurice L. , Taylor George W. , Shlossman Marc , Bennett Peter H. , Genco Robert , Knowler William C.
Published: March 2007

OBJECTIVE—Periodontal disease may contribute to the increased mortality associated with diabetes.

RESEARCH DESIGN AND METHODS—In a prospective longitudinal study of 628 subjects aged ≥35 years, we examined the effect of periodontal disease on overall and cardiovascular disease mortality in Pima Indians with type 2 diabetes. Periodontal abnormality was classified as no or mild, moderate, and severe, based on panoramic radiographs and clinical dental examinations.

RESULTS—During a median follow-up of 11 years (range 0.3–16), 204 subjects died. The age- and sex-adjusted death rates for all natural causes expressed as the number of deaths per 1,000 person-years of follow-up were 3.7 (95% CI 0.7–6.6) for no or mild periodontal disease, 19.6 (10.7–28.5) for moderate periodontal disease, and 28.4 (22.3–34.6) for severe periodontal disease. Periodontal disease predicted deaths from ischemic heart disease (IHD) (P trend = 0.04) and diabetic nephropathy (P trend < 0.01). Death rates from other causes were not associated with periodontal disease. After adjustment for age, sex, duration of diabetes, HbA1c, macroalbuminuria, BMI, serum cholesterol concentration, hypertension, electrocardiographic abnormalities, and current smoking in a proportional hazards model, subjects with severe periodontal disease had 3.2 times the risk (95% CI 1.1–9.3) of cardiorenal mortality (IHD and diabetic nephropathy combined) compared with the reference group (no or mild periodontal disease and moderate periodontal disease combined).

CONCLUSIONS— Periodontal disease is a strong predictor of mortality from IHD and diabetic nephropathy in Pima Indians with type 2 diabetes. The effect of periodontal disease is in addition to the effects of traditional risk factors for these diseases.
The Influence of Insulin Use on Glycemic Control
Authors: Cramer Joyce A. , Pugh Mary Jo
Published: March 2007

OBJECTIVE—The purposes of this study were to determine the relationship between insulin self-management and glycemic control and to identify patient characteristics associated with better control.

RESEARCH DESIGN AND METHODS—A Department of Veterans Affairs regional database was used to identify patients with diabetes on chronic insulin therapy (n = 6,222) with dose defined as number of units and doses. The rate of insulin use during a 2-year period was calculated using pharmacy data. Regression analyses were used 1) to predict compliance with prescribed insulin regimens using demographic variables, HbA1c levels, and a measure of diabetes management intensity and 2) to predict HbA1c levels using demographic variables and rates of insulin use.

RESULTS—Insulin use was 77.44 ± 17% of prescribed amounts, including wastage; HbA1c levels were 7.98 ± 1.66%. Concomitant oral hypoglycemic agent use (84.89 ± 16%) was higher than insulin use (P < 0.0001) but correlated with insulin use (r = 0.189, P < 0.0001). Ordinary least-squares regression showed that race, HbA1c levels, and intensity of diabetes management were significant predictors of insulin use. Age, race, and insulin use were significant predictors of HbA1c levels.

CONCLUSIONS—Adults prescribed a specific insulin regimen averaged using 77% of prescribed doses, demonstrating good intention to follow the prescription. However, HbA1c higher than the recommended level suggested that the rate of insulin use, the prescribed regimen, or both were inadequate to achieve good glycemic control in patients with long-term insulin use.
The Relationship of Disordered Eating Habits and Attitudes to Clinical Outcomes in Young Adult Females With Type 1 Diabetes
Authors: Peveler Robert C. , Bryden Kathryn S. , Neil H. Andrew W. , Fairburn Christopher G. , Mayou Richard A. , Dunger David B. , Turner Hannah M.
Published: March 2007

OBJECTIVE—To describe the clinical outcomes of adolescent and young adult female subjects with type 1 diabetes in relation to the disturbance of eating habits and attitudes over 8–12 years.

RESEARCH DESIGN AND METHODS—Patients were recruited from the registers of pediatric and young adult diabetes clinics (including nonattenders) and interviewed in the community. A total of 87 patients were assessed at baseline (aged 11–25 years), and 63 (72%) were reinterviewed after 8–12 years (aged 20–38 years). Eating habits and attitudes were assessed by a semistructured research diagnostic interview (Eating Disorder Examination).

RESULTS—Clinical eating disorders ascertained from the interview and/or case note review at baseline or follow-up were found in 13 subjects (14.9% [95% CI 8.2–24.2]), and an additional 7 subjects had evidence of bingeing or purging, bringing the total affected to 26%. Insulin misuse for weight control was reported by 31 (35.6% [25.7–46.6]) subjects. Overall outcome was poor; serious microvascular complications were common and mortality was high. There were significant relationships between disordered eating habits, insulin misuse, and microvascular complications.

CONCLUSIONS—Although the cross-sectional prevalence of clinical eating disorders in young women with diabetes is modest, the cumulative incidence of eating problems continues to increase after young adulthood, and this is strongly associated with poor physical health outcomes. The combination of an eating disorder and diabetes puts patients at high risk of mortality and morbidity. Better methods of detection and management are needed.
Glycemic Characteristics in Continuously Monitored Patients With Type 1 and Type 2 Diabetes
Authors: Bode Bruce W. , Schwartz Sherwyn , Stubbs Harrison A. , Block Jon E.
Published: March 2007

OBJECTIVE—The purpose of this study was to generate normative values for periods of euglycemia as well as for daily patterns of glycemic excursions in patients with type 1 and type 2 diabetes monitored continuously for a maximum period of 21 days and blinded to glucose levels.

RESEARCH DESIGN AND METHODS—This was a multicenter, prospective observational study in which 101 consecutive patients with type 1 (n = 60) or type 2 (n = 41) diabetes underwent blinded continuous glucose monitoring. Serial glucose measurements were divided into periods of euglycemia (70–180 mg/dl), hyperglycemia (>180 mg/dl), and hypoglycemia (<70 mg/dl). The proportions of time patients were hypoglycemic, euglycemic, and hyperglycemic and the total areas under the curves (AUCs) were determined.

RESULTS—During the observation period the 101 subjects contributed an average 287 ± 132 h of continuous glucose values. Subjects remained in the euglycemic range for ∼63% of the total day, were hypoglycemic 8%, and were hyperglycemic 29%. Hypoglycemia was more prevalent nocturnally (11 vs. 7%) and hyperglycemia diurnally (31 vs. 25%). Compared with subjects with type 2 diabetes, type 1 diabetic subjects had more frequent hypoglycemic episodes per day (2.1 vs. 1.0; P < 0.001) that were of longer duration (1.1 vs. 0.7 h; P < 0.0001), reflecting a greater number of hours per day in the hypoglycemic range (2.3 vs. 1.0 h; P < 0.0001). The mean hypoglycemic AUC values were >150% higher for type 1 compared with type 2 diabetic subjects (41 vs. 16, respectively; P < 0.0001).

CONCLUSIONS—These normative data will assist in study and sample size planning for future investigations of continuous glucose monitoring and allow for qualitative comparisons with trials of therapeutic interventions aimed at reducing the occurrence of glycemic excursions.
Lipid, Lipoproteins, C-Reactive Protein, and Hemostatic Factors at Baseline in the Diabetes Prevention Program
Authors:   the Diabetes Prevention Program Research Group
Published: March 2007

OBJECTIVE—Individuals with impaired glucose tolerance (IGT) appear to be at increased risk for cardiovascular disease (CVD) due at least in part to an increased prevalence of risk factors. We evaluated lipid, lipoprotein, C-reactive protein (CRP), fibrinogen, and tissue plasminogen activator (tPA) levels at study entry in the largest multiethnic cohort of participants with IGT described, namely in the Diabetes Prevention Program (DPP).

RESEARCH DESIGN AND METHODS—Measurements were performed at the baseline visit of 3,819 randomized participants of the DPP. Among 3,622 participants who were not taking lipid-lowering medicines, cardiovascular risk factors were analyzed in relation to demographic, anthropometric, and metabolic measures. Major determinants of risk factors were assessed in multivariate analysis.

RESULTS—Over 40% of participants had elevated triglyceride, LDL cholesterol, and CRP levels and reduced HDL cholesterol levels. Men had higher triglyceride and tPA and lower HDL cholesterol concentrations and smaller LDL particle size than women, whereas women had higher CRP and fibrinogen levels. African Americans had less dyslipidemia but higher fibrinogen levels, and Asian Americans had lower CRP and fibrinogen levels than Caucasians and Hispanics. The surrogate measure of insulin resistance (homeostasis model assessment of insulin resistance [HOMA-IR]) had the strongest association with HDL cholesterol, triglyceride, and tPA levels and LDL particle size. BMI had the greatest influence on CRP and fibrinogen levels. Using median splits of indexes of insulin resistance and insulin secretion (insulin-to-glucose ratio), participants with greater insulin resistance had a more adverse CVD risk-factor profile, whereas insulin secretion had little influence on risk factors.

CONCLUSIONS—The pattern of CVD risk factors in participants with IGT in the DPP exhibits substantial heterogeneity and is significantly influenced by race, sex, and age, as well as by obesity, glucose, and insulin measures. The degree of insulin resistance, as reflected by HOMA-IR, showed the greatest association with the cardiovascular risk factors.
Serum Ferritin Is Associated With Visceral Fat Area and Subcutaneous Fat Area
Authors: Iwasaki Tomoyuki , Nakajima Atsushi , Yoneda Masato , Yamada Yoshihiko , Mukasa Koji , Fujita Koji , Fujisawa Nobutaka , Wada Koichiro , Terauchi Yasuo
Published: March 2007

OBJECTIVE—Until now, few clinical studies have reported on the association between the indexes of body fat distribution and serum ferritin, an indicator of body iron stores and a putative risk factor for insulin resistance. We investigated the association between serum ferritin concentrations and the indexes of distribution of adipose tissues in the body, such as the visceral fat area (VFA), the subcutaneous fat area (SFA), and the hepatic fat content in Japanese subjects.

RESEARCH DESIGN AND METHODS—A total of 248 Japanese subjects (127 men and 121 postmenopausal women aged 57.8 ± 13.9 years, BMI 25.7 ± 4.6 kg/m2; 140 subjects with type 2 diabetes and 108 nondiabetic subjects) were evaluated. Subjects with a history of alcohol intake were excluded from the study. We measured body height, body weight, and serum ferritin, as well as fasting plasma glucose and plasma insulin concentrations. We estimated insulin resistance by homeostasis model assessment. The fat distribution was evaluated by measuring the VFA and SFA by abdominal computed tomography at the umbilical level. To assess the hepatic fat content, the ratio of the computed tomography attenuation value of the liver to that of the spleen was calculated.

RESULTS—Serum ferritin was significantly correlated with the various indexes of adiposity examined, such as the hepatic fat content (r = −0.280, P < 0.0001), VFA (r = 0.254, P < 0.0001), SFA (r = 0.231, P = 0.0005), and homeostasis model assessment (r = 0.286, P = 0.0008).

CONCLUSIONS—This is the first report to directly demonstrate an association between serum ferritin and VFA and SFA. The results of this study suggest that the serum ferritin concentration may be a useful indicator of systemic fat content and degree of insulin resistance.
Longitudinal Assessment of Quality of Life in Patients With Type 2 Diabetes and Self-Reported Erectile Dysfunction
Authors: De Berardis Giorgia , Pellegrini Fabio , Franciosi Monica , Belfiglio Maurizio , Di Nardo Barbara , Greenfield Sheldon , Kaplan Sherrie H. , Rossi Maria C.E. , Sacco Michele , Tognoni Gianni , Valentini Miriam , Nicolucci Antonio ,   on behalf of the QuED (Quality of Care and Outcomes in Type 2 Diabetes) Study Group
Published: March 2007

OBJECTIVE—In the context of the QuED (Quality of Care and Outcomes in Type 2 Diabetes) project, we evaluated the longitudinal changes over 3 years in quality of life (QoL) in patients with type 2 diabetes according to the presence or the development of erectile dysfunction (ED).

RESEARCH DESIGN AND METHODS—Patients were requested to fill in a questionnaire investigating the presence of ED and QoL (SF-36 Health Survey, depression symptoms [Center for Epidemiologic Studies–Depression], and quality of sexual life) every 6 months for 3 years. The analyses were based on multilevel models, adjusted for patient clinical and sociodemographic characteristics.

RESULTS—The study involved 1,456 patients, of whom 34% reported frequent erectile problems at baseline; 192 developed ED during the follow-up. No changes in QoL measures were detected in patients without ED; in those with ED at baseline, a worsening in all SF-36 scales was observed, reaching statistical significance for physical functioning (P = 0.03). Among patients who developed ED during the study, a deterioration in all SF-36 dimensions and a worsening in depressive symptoms preceded the development of ED. The onset of ED was associated with a further marked worsening in physical functioning (P = 0.0008), general health perception (P = 0.02), and social functioning (P = 0.04) on SF-36 subscales, as well as in the summary physical and mental components scores (P = 0.04 and P = 0.07, respectively). The development of ED was also associated with a highly significant increase in depressive symptoms (P = 0.001) and a marked decrease in quality of sexual life (P < 0.0001).

CONCLUSIONS—This longitudinal study documents for the first time the impact of ED onset on several aspects of QoL in patients with type 2 diabetes. The study also shows that QoL tended to further decrease during 3 years in patients with ED at baseline but not in those without this condition.
Increasing the Decrement in Insulin Secretion Improves Glucagon Responses to Hypoglycemia in Advanced Type 2 Diabetes
Authors: Israelian Zarmen , Gosmanov Niyaz R. , Szoke Ervin , Schorr Manju , Bokhari Syed , Cryer Philip E. , Gerich John E. , Meyer Christian
Published: March 2007

OBJECTIVE—In advanced β-cell failure, counterregulatory glucagon responses may be impaired due to a reduced decrement in insulin secretion during the development of hypoglycemia. The present studies were therefore undertaken to test the hypothesis that these may be improved by increasing this decrement in insulin secretion.

RESEARCH DESIGN AND METHODS—Twelve subjects with type 2 diabetes who have been insulin requiring were studied as a model of advanced β-cell failure. Glucagon responses were examined during a 90-min hypoglycemic clamp (∼2.8 mmol/l) on two separate occasions. On one occasion, tolbutamide was infused for 2 h before the clamp so that the decrement in insulin secretion during the induction of hypoglycemia would be increased. On the other occasion, normal saline was infused as a control.

RESULTS—Before the hypoglycemic clamp, infusion of tolbutamide increased insulin secretion ∼1.9-fold (P < 0.001). However, during hypoglycemia, insulin secretion decreased to similar rates on both occasions (P = 0.31) so that its decrement was approximately twofold greater following the tolbutamide infusion (1.63 ± 0.20 vs. 0.81 ± 0.17 pmol · kg−1 · min−1, P < 0.001). This was associated with more than twofold-greater glucagon responses (42 ± 11 vs. 19 ± 8 ng/l, P < 0.002) during the hypoglycemic clamp but unaltered glucagon responses to intravenous arginine immediately thereafter (449 ± 50 vs. 453 ± 50 ng/l, P = 0.78).

CONCLUSIONS—Increasing the decrement in insulin secretion during the development of hypoglycemia improves counterregulatory glucagon responses in advanced β-cell failure. These findings further support the concept that the impaired counterregulatory glucagon responses in advanced β-cell failure may at least partially be due to a reduced decrement in insulin secretion.
A Randomized Controlled Trial of the Effect of Real-Time Telemedicine Support on Glycemic Control in Young Adults With Type 1 Diabetes (ISRCTN 46889446)
Authors: Farmer Andrew J. , Gibson Oliver J. , Dudley Christina , Bryden Kathryn , Hayton Paul M. , Tarassenko Lionel , Neil Andrew
Published: March 2007

OBJECTIVE—To determine whether a system of telemedicine support can improve glycemic control in type 1 diabetes.

RESEARCH DESIGN AND METHODS—A 9-month randomized trial compared glucose self-monitoring real-time result transmission and feedback of results for the previous 24 h in the control group with real-time graphical phone-based feedback for the previous 2 weeks together with nurse-initiated support using a web-based graphical analysis of glucose self-monitoring results in the intervention group. All patients aged 18–30 years with HbA1c (A1C) levels of 8–11% were eligible for inclusion.

RESULTS—A total of 93 patients (55 men) with mean diabetes duration (means ± SD) 12.1 ± 6.7 years were recruited from a young adult clinic. In total, the intervention and control groups transmitted 29,765 and 21,400 results, respectively. The corresponding median blood glucose levels were 8.9 mmol/l (interquartile range 5.4–13.5) and 10.3 mmol/l (6.5–14.4) (P < 0.0001). There was a reduction in A1C in the intervention group after 9 months from 9.2 ± 1.1 to 8.6 ± 1.4% (difference 0.6% [95% CI 0.3–1.0]) and a reduction in A1C in the control group from 9.3 ± 1.5 to 8.9 ± 1.4% (difference 0.4% [0.03–0.7]). This difference in change in A1C between groups was not statistically significant (0.2% [−0.2 to 0.7, P = 0.3).

CONCLUSIONS—Real-time telemedicine transmission and feedback of information about blood glucose results with nurse support is feasible and acceptable to patients, but to significantly improve glycemic control, access to real-time decision support for medication dosing and changes in diet and exercise may be required.