bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic Control in Adolescent Girls
Authors: Maharaj Sherry , Daneman Denis , Olmsted Marion , Rodin Gary
Published: March 2007

OBJECTIVE—This study investigated whether intimacy and autonomy in mother-daughter interactions and relational aspects of the self are associated with metabolic control in adolescent girls with type 1 diabetes.

RESEARCH DESIGN AND METHODS—This cross-sectional study included 88 girls with diabetes (mean age 14.9 ± 2.2 years, diabetes duration 7.1 ± 3.9 years, and HbA1c 8.9 ± 1.6%) from the Diabetes Clinic at the Hospital for Sick Children in Toronto and their mothers. Teens completed a self-report measure assessing self-concept in eight domain-specific areas. Mothers and daughters engaged in a 7-min, videotaped, problem-solving task involving a diabetes-related conflict issue. Interactions were rated using a macroanalytic rating system to assess intimacy and autonomy in parent-teen relationships. Metabolic control was measured using HbA1c.

RESULTS—Self-concept in domains of perceived behavioral conduct (P = 0.003), social acceptance (P = 0.03), romantic appeal (P = 0.03), and close friendships (P = 0.04) independently predicted HbA1c levels, together accounting for 30% of the variance. Also, the experience of emotional closeness (i.e., intimacy) rather than separateness (i.e., autonomy) in mother-daughter relationships was associated with lower HbA1c (P = 0.03).

CONCLUSIONS—Relational aspects of the self and the experience of emotional closeness in relationships are associated with metabolic control in adolescent girls. Efforts to improve metabolic control in girls should include enhancing the self-concept and the experience of relatedness in familial, peer, and patient-caregiver relationships.
Adiponectin Is Associated With Vascular Function Independent of Insulin Sensitivity
Authors: Fernández-Real José-Manuel , Castro Antoni , Vázquez Gabriel , Casamitjana Roser , López-Bermejo Abel , Peñarroja Georgina , Ricart Wifredo
Published: March 2007

OBJECTIVE—Adiponectin has been proposed to play important roles in the regulation of energy homeostasis and insulin sensitivity. In experimental studies, adiponectin has also been found to inhibit vascular smooth muscle cell proliferation. Decreased adiponectin levels have been described in patients with coronary artery disease, and circulating adiponectin predicts cardiovascular death in patients with renal failure. Because adiponectin appears to influence both insulin sensitivity and vessel wall physiology, we examined insulin sensitivity and vascular function in relation with circulating adiponectin.

RESEARCH DESIGN AND METHODS—We studied brachial artery vascular reactivity (high-resolution external ultrasound) and insulin sensitivity (minimal model) in 68 healthy subjects. Brachial artery vascular reactivity was also determined in 52 patients with altered glucose tolerance: 30 subjects with impaired fasting glucose (IFG) or glucose intolerance (GIT) and 22 patients with type 2 diabetes.

RESULTS—Circulating adiponectin concentration was significantly associated with insulin sensitivity (r = 0.29, P = 0.02) and with fasting serum triglycerides (r = −0.29, P = 0.02) in healthy subjects. In the latter, adiponectin levels were positively associated with arterial vasodilation in response to nitroglycerin (endothelium-independent vasodilation [EIVD], r = 0.41, P = 0.002) but not with flux-induced, endothelium-dependent vasodilation (EDVD) (r = 0.007, P = NS). In contrast, EIVD was not significantly associated with adiponectin in subjects with IFG, GIT, or type 2 diabetes (r ≤ 0.10, P = NS). In a multiple linear regression analysis to predict EIVD in healthy subjects, age (P = 0.012), sex (P = 0.042), and adiponectin concentration (P = 0.045), but not BMI, insulin sensitivity, or fasting triglycerides, contributed to 39% of EIVD variance.

CONCLUSIONS—Serum adiponectin concentration appears to be significantly associated with vascular function in apparently healthy humans. This association seems to be independent of its link with insulin sensitivity.
Adult-Onset Atypical (Type 1) Diabetes
Authors: Aguilera Eva , Casamitjana Roser , Ercilla Guadalupe , Oriola Josep , Gomis Ramon , Conget Ignacio
Published: March 2007

OBJECTIVE—In 1997, the American Diabetes Association proposed two subcategories for type 1 diabetes: type 1A or immunomediated diabetes and type 1B or idiopathic diabetes characterized by negative β-cell autoimmunity markers, lack of association with HLA, and fluctuating insulinopenia. The aim of this study was to examine clinical characteristics, β-cell function, HLA typing, and mutations in maturity-onset diabetes of the young (MODY) genes in patients with atypical type 1 diabetes (type 1 diabetes diagnosed at onset, without pancreatic autoantibodies and fluctuating insulinopenia).

RESEARCH DESIGN AND METHODS—Eight patients with atypical type 1 diabetes (all men, 30.7 ± 7.6 years) and 16 newly diagnosed age- and sex-matched patients with type 1A diabetes were studied retrospectively. Islet cell, GAD, tyrosine phosphatase and insulin antibodies, and basal and stimulated plasma C-peptide were measured at onset and after 1 year. HLA-DRB1-DQA1-DQB1 typing and screening for mutations in the HNF-1α and HNF-4α genes were performed from genomic DNA.

RESULTS—Atypical patients displayed significantly higher BMI and better β-cell function at onset and after 12 months. Three patients carried protective or neutral type 1 diabetes haplotypes, five patients displayed heterozygosity for susceptible and protective haplotypes, and seven patients showed Aspβ57. We found a nondescribed variant Pro436Ser in exon 10 of the HNF-4α gene in one atypical patient without susceptible haplotypes.

CONCLUSIONS—In our population, there are atypical forms of young adult-onset ketosis-prone diabetes initially diagnosed as type 1 diabetes, differing from type 1 diabetes in the absence of β-cell autoimmunity, persistent β-cell function capacity, fluctuating insulin requirements and ketosis-prone episodes, as well as clinical features of type 2 diabetes. Only one subgroup could be strictly classified as having type 1B diabetes. Additional information is still needed to improve our understanding of the mechanisms that finally lead to the disease.
Increasing Severity of Cardiovascular Risk Factors With Increasing Middle Cerebral Artery Stenotic Involvement in Type 2 Diabetic Chinese Patients With Asymptomatic Cerebrovascular Disease
Authors: Thomas G. Neil , Lin Jian Wen , Lam Wynnie W.M. , Tomlinson Brian , Yeung Vincent , Chan Juliana C.N. , Liu Roxanna , Wong Ka Sing
Published: March 2007

OBJECTIVE—To identify determinants associated with increasing severity of middle cerebral artery (MCA) stenosis in asymptomatic Chinese type 2 diabetic patients with and without MCA stenosis determined using transcranial Doppler. Conventional risk factors contribute to the pathogenesis of ischemic stroke, and differences in the pattern of these may explain the heterogeneity of disease presentation in different populations. In Chinese patients, MCA stenosis is the most commonly identified intracranial vascular lesion.

RESEARCH DESIGN AND METHODS—Anthropometric and fasting biochemical parameters were compared between type 2 diabetic patients with MCA stenosis in one (n = 185) or both (n = 200) vessels and 1,492 type 2 diabetic patients without evidence of stenosis.

RESULTS—Increasing MCA stenotic vascular involvement was associated with significantly increasing age, duration of diabetes, systolic blood pressure, and LDL cholesterol, but with lower glucose levels. There was also an increased prevalence of hypertension, dyslipidemia, and use of blood pressure–and glucose-lowering agents in the patients with MCA stenosis. Concomitant significant increases in the prevalence of peripheral vascular disease and retinopathy were also observed in the patients with MCA stenosis.

CONCLUSIONS—Transcranial Doppler examination identified stenosis in one or both MCAs in over one-fifth of the Chinese type 2 diabetic subjects without symptoms of cerebrovascular disease. A number of conventional cardiovascular risk factors were closely associated with MCA stenosis. This technique may allow the identification of a particularly high-risk group, and further studies are required to determine whether asymptomatic MCA stenosis is predictive of primary cerebrovascular events and whether intensive treatment of risk factors would reduce the risk.
Impaired Insulin Sensitivity, Insulin Secretion, and Glucose Effectiveness Predict Future Development of Impaired Glucose Tolerance and Type 2 Diabetes in Pre-Diabetic African Americans
Authors: Osei Kwame , Rhinesmith Scott , Gaillard Trudy , Schuster Dara
Published: March 2007

OBJECTIVE—We examined the determinants of impaired glucose tolerance (IGT) and type 2 diabetes in first-degree relatives of African-American type 2 diabetic patients over 5–8 years (median 6).

RESEARCH DESIGN AND METHODS—A total of 81 healthy subjects (age 41.5 ± 4.8 years; BMI 31.3 ± 3.6 kg/m2) participated in the study. Each subject underwent an oral glucose tolerance test (OGTT) and a frequently sampled intravenous glucose tolerance test at baseline. Insulin sensitivity index (Si) and glucose effectiveness index (Sg) were determined by the minimal model method. Homeostasis model assessment (HOMA) was used to estimate insulin resistance (HOMA-IR) and β-cell function (HOMA-%B). A total of 18 subjects progressed to either IGT or type 2 diabetes (progressors), whereas 19 subjects maintained normal glucose tolerance (nonprogressors).

RESULTS—Comparing the progressors and nonprogressors, mean fasting serum glucose levels (95 ± 8 vs. 80 ± 14 mg/dl, P < 0.01) and 2-h serum glucose levels (149 ± 27 vs. 100 ± 60 mg/dl, P < 0.01) as well as 2-h serum insulin levels (117 ± 81 vs. 72 ± 87 μU/ml, P < 0.01) during OGTT were higher at baseline. Mean acute first-phase insulin secretion (205 ± 217 vs. 305 ± 230 μU/ml), HOMA-%B (148 ± 60 vs. 346 ± 372, P < 01), Si (1.61 ± 1.13 vs. 2.48 ± 1.25 × 10−4 · min−1 [μU/ml]−1), and Sg (1.48 ± 0.61 vs. 2.30 ± 0.97 × 10−2 · min−1) were lower in the progressors than in the nonprogressors at baseline. Mean HOMA-IR (3.31 ± 1.64 vs. 2.36 ± 1.64) was significantly greater in the progressors than the nonprogressors. At the time of diagnosis of glucose intolerance (IGT + diabetes), HOMA-%B (101 ± 48 vs. 148 ± 60, P < 0.001) and HOMA-IR (5.44 ± 2.55 vs. 3.31 ± 1.64, P < 0.003) deteriorated in the progressors versus baseline.

CONCLUSIONS—We conclude that nondiabetic, first-degree relatives of African-American type 2 diabetic patients who progressed to IGT and type 2 diabetes manifest triple defects (decreased insulin secretion, insulin action, and glucose effectiveness) that antecede the disease.
Impact of Achilles Tendon Lengthening on Functional Limitations and Perceived Disability in People With a Neuropathic Plantar Ulcer
Authors: Mueller Michael J. , Sinacore David R. , Hastings Mary Kent , Lott Donovan J. , Strube Michael J , Johnson Jeffrey E.
Published: March 2007

OBJECTIVE—An Achilles tendon-lengthening (ATL) procedure is effective at reducing ulcer recurrence in patients with diabetes, peripheral neuropathy, and a plantar ulcer, but its effects on functional limitations and perceived disability are unknown. The purpose of this study is to report the effects of an ATL and total contact casting (TCC) on the functional limitations and perceived disability of patients with neuropathic plantar ulcers.

RESEARCH DESIGN AND METHODS—Twenty-eight subjects with a mean age of 55 ± 10 years and a BMI of 33 ± 6 kg/m2 participated. All subjects had a history of diabetes, loss of protective sensation, limited ankle motion, and a recurrent forefoot ulcer. Subjects were randomized into two groups: an ATL group (n = 14), who received treatment of ATL, and TCC and a TCC group (n = 14), who received TCC only. Subjects completed a modified physical performance test (PPT) and the SF-36 Health Survey before treatment, after primary treatment and healing of the plantar forefoot ulcer, and 8 months after initial ulcer healing.

RESULTS—There were no significant changes in functional limitations as measured by the PPT between groups or over time. The physical summary score of the SF-36 decreased slightly from before treatment to 8 months after initial ulcer healing in the ATL group (35 ± 7 to 31 ± 6), whereas the TCC group score increased during this time (34 ± 8 to 39 ± 11; P < 0.05).

CONCLUSIONS—The ATL resulted in no measurable change in functional limitations, but patients receiving an ATL and TCC reported lower physical functioning at 8 months after initial ulcer healing than subjects receiving TCC alone and may require additional physical therapy to address this perceived disability.
Nationwide, Prospective Registration of Type 1 Diabetes in Children Aged <15 Years in Norway 1989–1998
Authors: Joner Geir , Stene Lars C. , Søvik Oddmund ,   the Norwegian Childhood Diabetes Study Group
Published: March 2007

OBJECTIVE—An increasing incidence rate of childhood-onset type 1 diabetes has been described in several countries, particularly among the youngest children, and the Nordic countries have consistently been shown to have the highest incidence rates. An increasing incidence had previously been reported in Norway for 1973–1982, together with regional variation within the country. The aim of this study was to test whether there has been an increasing incidence of type 1 diabetes and a continued regional variation among children aged <15 years in Norway during 1989–1998.

RESEARCH DESIGN AND METHODS—As a part of the activities of the National Childhood Diabetes Registry of Norway and the EURODIAB study, a 10-year prospective, nationwide case registration of type 1 diabetes was done among children aged <15 years.

RESULTS—A total of 1,867 new case subjects (1,009 boys and 858 girls) were identified. The total incidence rate was 22.4 per 100,000 person-years (95% CI 21.5–23.5). The incidence was 13.1, 26.3, and 28.8 per 100,000 in the age-groups 0–4.9, 5–9.9, and 10–14.9 years, respectively. No increase or decrease over time was detected in any of the age-groups during the 10-year period. We found significant variation between the 19 counties, which only partly reflected the pattern previously described for 1973–1982.

CONCLUSIONS—We found a significant regional variation within Norway. After a previous period of increase, the incidence has been stable in all age-groups <15 years during 1989–1998.
The Effect of Pioglitazone on Peroxisome Proliferator-Activated Receptor-γ Target Genes Related to Lipid Storage In Vivo
Authors: Bogacka Iwona , Xie Hui , Bray George A. , Smith Steven R.
Published: March 2007

OBJECTIVE—Pioglitazone is a member of the thiazolidinediones (TZDs), insulin-sensitizing agents used to treat type 2 diabetes. The aim of this study was to define the effect of pioglitazone on the expression of genes related to carbohydrate and lipid metabolism in subcutaneous fat obtained from type 2 diabetic patients.

RESEARCH DESIGN AND METHODS—Forty-eight volunteers with type 2 diabetes were divided into two groups treated for 12 weeks with placebo or pioglitazone (30 mg/day). The expression of several genes was quantified by real-time RT-PCR.

RESULTS—Pioglitazone treatment increased the expression of genes involved in glycerol-3-phosphate synthesis. The mRNA expression of PEPCK-C and glycerol-3-phosphate dehydrogenase (GPDH) increased (P < 0.01) in patients treated with pioglitazone. There was no difference in glycerol kinase (GyK) mRNA levels. The expression of genes that regulate fatty acid availability in adipocytes, including lipoprotein lipase (LPL) and acetyl-CoA synthetase (ACS), was higher (P < 0.01) in pioglitazone-treated patients. Pioglitazone stimulated (P < 0.0001) expression of c-Cbl-associated protein (CAP), whereas tumor necrosis factor-α, leptin, resistin, angiopoietin like-4, and 11-β-hydroxysteroid dehydrogenase type 1 (11β HSD 1) were not affected by pioglitazone. The baseline peroxisome proliferator-activated receptor (PPAR)-γ1 mRNA was significantly correlated with mRNA for LPL, CAP, ACS, 11β HSD 1, GyK, fatty acid synthase, leptin, and GPDH, whereas PPAR-γ2 mRNA was correlated with CAP, PEPCK-C, leptin, and GPDH.

CONCLUSIONS—Treatment with pioglitazone increased body weight, and this is associated with upregulation of some, but not all, genes previously demonstrated as “TZD responsive” in subcutaneous fat. The results suggest that TZDs might increase body weight through the upregulation of genes facilitating adipocyte lipid storage in vivo.
Non-HDL Cholesterol and Apolipoprotein B Predict Cardiovascular Disease Events Among Men With Type 2 Diabetes
Authors: Jiang Rui , Schulze Matthias B. , Li Tricia , Rifai Nader , Stampfer Meir J. , Rimm Eric B. , Hu Frank B.
Published: March 2007

OBJECTIVE—To evaluate the role of non-HDL cholesterol and apolipoprotein (apo)B, markers of all potentially atherogenic lipoproteins, as predictors of cardiovascular disease (CVD) in comparison with LDL cholesterol in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS—We prospectively followed 746 diabetic men in the Health Professionals’ Follow-up Study who were aged 46–81 years and free of CVD or cancer at the time of blood draw in 1993–1994. During 6 years of follow-up, we ascertained 103 incident CVD cases.

RESULTS—We used Cox proportional hazard modeling to estimate the relative risk (RR) of CVD. After adjustment for age, BMI, and other lifestyle risk factors, the multivariate RR of CVD (the highest versus the lowest quartile) was 2.34 (95% CI 1.26–4.32) for non-HDL cholesterol, 2.31 (1.23–4.35) for apoB, and 1.74 (0.99–3.06) for LDL cholesterol. Comparisons of nested models indicate that non-HDL cholesterol, but not apoB, adds significantly to the prediction of CVD risk beyond LDL cholesterol. The area under the receiver operating characteristic curve was 0.685, 0.691, 0.695, and 0.722 for the CVD risk-prediction model with LDL cholesterol, apoB, non-HDL cholesterol, and total cholesterol–to–HDL cholesterol ratio (or the non-HDL–to–HDL cholesterol ratio), respectively.

CONCLUSIONS—Non-HDL cholesterol and apoB are more potent predictors of CVD incidence among diabetic men than LDL cholesterol. Statistically, the ratio of total to HDL cholesterol is the best predictor of CVD in this cohort of diabetic men.
Phenotype-Genotype Correlations in a Series of Wolfram Syndrome Families
Authors: Smith Casey J.A. , Crock Patricia A. , King Bruce R. , Meldrum Cliff J. , Scott Rodney J.
Published: March 2007

OBJECTIVE—Wolfram syndrome is an extremely rare autosomal-recessive disorder that predisposes the development of type 1 diabetes in association with progressive optic atrophy. The genetic basis of this disease has been shown to be due to mutations in the WFS1 gene. The WFS1 gene encodes a novel transmembrane protein called wolframin, which recent evidence suggests may serve as a novel endoplasmic reticulum calcium channel in pancreatic β-cells and neurons. Genotype-phenotype correlations in this syndrome are becoming apparent and may help in explaining some of the variable characteristics observed in this disease.

RESEARCH DESIGN AND METHODS—In this report, we have studied 13 patients with Wolfram syndrome from nine families to further define the relationship between mutation site and type with specific disease characteristics.

RESULTS—A severe phenotype was seen in patients with mutations in exon 4 and with a large deletion encompassing most of exon 8. In total, nine novel mutations were identified as well as three new silent polymorphisms.

CONCLUSIONS—Similar to all other mutation reports, most causative changes identified in the WFS1 gene occurred in exon 8, and only one was identified outside this region in exon 4.
Increased Utilization of Primary Care 5 Years Before Diagnosis of Type 2 Diabetes
Authors: Gulliford Martin C. , Charlton Judith , Latinovic Radoslav
Published: March 2007

OBJECTIVE—To determine whether case subjects who were later diagnosed with type 2 diabetes utilized primary care differently from control subjects who remained free from diabetes.

RESEARCH DESIGN AND METHODS—We conducted a matched cohort study using the U.K. General Practice Research Database. Case subjects were aged 30–89 years, diagnosed with diabetes, and later prescribed oral hypoglycemic drugs between 1997 and 2000. Control subjects, who were matched for age, sex, and general practice, were not diagnosed with diabetes and not treated with oral hypoglycemic drugs or insulin.

RESULTS—Data were analyzed for 5,158 case subjects (2,492 women and 2,666 men) and their matched control subjects with a mean age of 63 years. Five years before the date of diagnosis, case subjects consulted more frequently than control subjects (rate ratio [RR] 1.26 [95% CI 1.20–1.33]) and received more prescription items (1.44 [1.36–1.53]). Consultations were increased for a wide range of conditions. The cumulative 5-year prevalence of diagnoses of hypertension or treatment, hyperlipidemia or treatment, obesity, or coronary heart disease or stroke was 66.1% in case subjects and 45.9% in control subjects (1.44 [1.40–1.49]). A medical diagnosis of hyperglycemia or impaired glucose tolerance was highly (>99%) specific for later diagnosis of diabetes.

CONCLUSIONS—Primary care consultations and drug utilization are increased from 5 years before diagnosis of diabetes. Diagnoses of hypertension, hyperlipidemia, obesity, or coronary heart disease or stroke have moderate sensitivity for subsequent diabetes but are nonspecific. A diagnosis of hyperglycemia has a high specificity for later detection of diabetes.
Elevated C-Reactive Protein Is a Predictor of the Development of Diabetes in a General Japanese Population
Authors: Doi Yasufumi , Kiyohara Yutaka , Kubo Michiaki , Ninomiya Toshiharu , Wakugawa Yoshiyuki , Yonemoto Koji , Iwase Masanori , Iida Mitsuo
Published: March 2007

OBJECTIVE—We examined the association between high-sensitivity C-reactive protein (CRP) levels and the development of diabetes in a general Japanese population.

RESEARCH DESIGN AND METHODS—A total of 1,759 Japanese subjects, aged 40–79 years and without diabetes (according to American Diabetes Association fasting criteria), were stratified into three groups according to CRP tertiles by sex and followed up prospectively for a mean of 9.0 years.

RESULTS—During the follow-up, 131 subjects (67 men and 64 women) developed diabetes. In both sexes, the age-adjusted cumulative incidence of diabetes increased significantly as the tertiles of CRP levels increased. In multivariate analyses, the risk of developing diabetes was significantly higher in the highest CRP tertile than in the lowest after adjustment for a number of confounding factors (odds ratio 2.63 [95% CI 1.23–5.65] for men and 2.25 [1.01–5.01] for women). In stratified analyses, this CRP-diabetes association was stronger in subjects without obesity or other risk factors related to insulin resistance and in nondrinking subjects.

CONCLUSIONS—Our findings suggest that elevated CRP concentration is a significant predictor of diabetes in the general Japanese population, independent of obesity and insulin resistance.
Sleep Disturbances in Midlife Unrelated to 32-Year Diabetes Incidence
Authors: Björkelund Cecilia , Bondyr-Carlsson Dorota , Lapidus Leif , Lissner Lauren , Månsson Jörgen , Skoog Ingmar , Bengtsson Calle
Published: March 2007

OBJECTIVE—To study the relation between diabetes incidence and sleep problems in a population-based sample of women followed for 32 years.

RESEARCH DESIGN AND METHODS—The researchers conducted a prospective population study initiated in 1968–1969, with follow-ups in 1974–1975, 1980–1981, 1992–1993, and 2000–2001 in Gothenburg, Sweden. A total of 1,462 women born in 1908, 1914, 1918, 1922, and 1930, representative of women of the same ages in the general population, initially participated (90% participation rate). Reported sleep duration, sleep problems, and use of sleeping medication were related to incident diabetes from 1968 to 2000. Associations between sleep problems and diabetes were corrected for waist-to-hip ratio (WHR), BMI, subscapular skinfold, fasting blood glucose and serum lipid concentrations, blood pressure, heart rate, smoking, physical activity, education, and socioeconomic status. Additionally, associations between BMI, WHR, and sleep problems were examined.

RESULTS—Over 32 years, 126 women (8.7%) developed diabetes. Associations between diabetes and initial sleep problems were tested in a Cox regression analysis, taking into consideration factors associated (P < 0.1) with diabetes. Sleep problems in 1968 did not increase risk of developing diabetes during the following 32 years. Obesity, particularly centralized, was associated with sleep problems.

CONCLUSIONS—No association between sleep problems and developing diabetes was seen in this 32-year follow-up of middle-aged women. Obesity, on the other hand, known to cause increased risk of diabetes, was associated with current sleep problems.
Decreasing the Risk of Diabetic Retinopathy in a Study of Case Management
Authors: Pettitt David J. , Okada Wollitzer Alison , Jovanovic Lois , He Guozhong , Ipp Eli ,   the California Medi-Cal Type 2 Diabetes Study Group
Published: March 2007

OBJECTIVE—Diabetic retinopathy affects >60% of people with type 2 diabetes during the first 2 decades of the disease and is ameliorated by good glycemic control. This study tested whether intensive diabetes case management could prevent or delay diabetic retinopathy in patients with established type 2 diabetes.

RESEARCH DESIGN AND METHODS—This study was part of a randomized, controlled clinical trial of diabetes case management in type 2 diabetes in southern California counties serving low income ethnic minority populations. Subjects were randomized to intervention (diabetes case management) or control (traditional treatment) groups. Subjects with at least two retinal photographs (n = 149) were included in this analysis to assess the effect of intervention on development or progression of diabetic retinopathy.

RESULTS—Progression of retinopathy in the intervention group was not significantly less than in the control group (P = 0.226). However, those in the intervention group with no evidence of retinopathy at baseline were less likely to develop diabetic retinal changes (5/48) during a mean follow-up of 23.1 months than those in the control group (10/34, χ2 = 4.805, P = 0.028). This difference remained significant in a logistic regression model that controlled for potential confounders (odds ratio 5.35 [95% CI 1.14–25.12]).

CONCLUSIONS—This study shows that a relatively short duration of case management instituted before the onset of clinically identifiable retinopathy significantly diminished the risk of developing retinopathy in patients with type 2 diabetes. The findings also emphasized the retinal disease burden in this population, with development and progression of retinopathy occurring in <2 years.
Epidemiology of Ischemic Stroke in Patients With Diabetes
Authors: Kissela Brett M. , Khoury Jane , Kleindorfer Dawn , Woo Daniel , Schneider Alexander , Alwell Kathleen , Miller Rosemary , Ewing Irene , Moomaw Charles J. , Szaflarski Jerzy P. , Gebel James , Shukla Rakesh , Broderick Joseph P.
Published: March 2007

OBJECTIVE— Diabetes is a well known risk factor for stroke, but the impact of diabetes on stroke incidence rates is not known. This study uses a population-based study to describe the epidemiology of ischemic stroke in diabetic patients.

RESEARCH DESIGN AND METHODS— Hospitalized cases were ascertained by ICD-9 discharge codes, prospective screening of emergency department admission logs, and review of coroner’s cases. A sampling scheme was used to ascertain cases in the out-of-hospital setting. All potential cases underwent detailed chart abstraction by study nurses followed by physician review. Diabetes-specific incidence rates, case fatality rates, and population-attributable risks were estimated.

RESULTS— Ischemic stroke patients with diabetes are younger, more likely to be African American, and more likely to have hypertension, myocardial infarction, and high cholesterol than nondiabetic patients. Age-specific incidence rates and rate ratios show that diabetes increases ischemic stroke incidence at all ages, but this risk is most prominent before age 55 in African Americans and before age 65 in whites. One-year case fatality rates after ischemic stroke are not different between those patients with and without diabetes.

CONCLUSIONS— Given the “epidemic” of diabetes, with substantially increasing diabetes prevalence each year across all age- and race/ethnicity groups, the significance of diabetes as a risk factor for stroke is becoming more evident. Diabetes is clearly one of the most important risk factors for ischemic stroke, especially in those patients less than 65 years of age. We estimate that 37–42% of all ischemic strokes in both African Americans and whites are attributable to the effects of diabetes alone or in combination with hypertension.
Reduced Prevalence of Limited Joint Mobility in Type 1 Diabetes in a U.K. Clinic Population Over a 20-Year Period
Authors: Lindsay John R. , Kennedy Laurence , Atkinson A. Brew , Bell Patrick M. , Carson Dennis J. , McCance David R. , Hunter Steven J.
Published: March 2007

OBJECTIVE—Limited joint mobility (LJM), one of the earliest clinically apparent long-term complications of type 1 diabetes, is a risk marker for subsequent microvascular complications. We hypothesize that the prevalence of LJM may have decreased during the past two decades due to improved standards of glycemic control.

RESEARCH DESIGN AND METHODS—A single observer performed a survey in 204 consecutive patients with type 1 diabetes (106 men and 98 women, age 27 ± 1 years, HbA1c 8.3 ± 0.1%, duration of diabetes 14.5 ± 0.8 years, insulin dose 63 ± 2 units/day). We used the same examination method and criteria for assessment of LJM as used by us in an earlier study in 1981–1982.

RESULTS—The prevalence of LJM has fallen from 43 to 23% between the 1980s and 2002 (P < 0.0001). The relative risk for LJM in 2002 compared with the 1981–1982 cohort was 0.53 (0.40 < RR < 0.72, P < 0.0001). The prevalence of LJM was increased with longer duration of diabetes (<10 years, 13%; 10–20 years, 19%; 20–29 years, 30%; >30 years, 65%; P < 0.001). The relative risk for those with a mean HbA1c <7% in 2002 was 0.3 (0.1 < RR < 1.2, P = 0.05) when compared with those with mean HbA1c >7%.

CONCLUSIONS—The present study confirms the hypothesis that the prevalence of LJM is lower than 20 years ago and that improved standards of glycemic control and diabetes care may have contributed to this occurrence. Joint limitation in type 1 diabetes is strongly associated with duration of diabetes. The presence of LJM remains a common and important clinical marker for subsequent microvascular disease and can be a useful clinical tool for identification of patients at increased risk.
Twice-Weekly Progressive Resistance Training Decreases Abdominal Fat and Improves Insulin Sensitivity in Older Men With Type 2 Diabetes
Authors: Ibañez Javier , Izquierdo Mikel , Argüelles Iñaki , Forga Luis , Larrión José L. , García-Unciti Marisol , Idoate Fernando , Gorostiaga Esteban M.
Published: March 2007

OBJECTIVE—To evaluate the influence of a twice-weekly progressive resistance training (PRT) program, without a concomitant weight loss diet, on abdominal fat and insulin sensitivity in older men with type 2 diabetes.

RESEARCH DESIGN AND METHODS—Nine older men (aged 66.6 ± 3.1) with type 2 diabetes participated in a 16-week PRT supervised program (50–80% of the one repetition maximum), for all main muscle groups. Basal glycemia, HbA1c, diet, habitual physical activity, body composition, and upper/lower maximal strength were measured. Insulin sensitivity was determined according to Bergman’s minimal model procedure and abdominal fat was obtained by computed tomography. The measurements were taken 4 weeks before training (−4), immediately before training (0), and at 8-week intervals (i.e., weeks 8 and 16) during the 16-week training period.

RESULTS—No significant variation was observed in any of the above selected parameters during the 4-week control period. After PRT, both leg and arm maximal strength increased significantly by 17.1 and 18.2%, respectively. Visceral and subcutaneous abdominal fat decreased significantly by 10.3% (from 249.5 ± 97.9 to 225.6 ± 96.6 cm3, P < 0.01) and by 11.2% (from 356.0 ± 127.5 to 308.6 ± 118.8 cm3, P < 0.01), respectively, while no changes were observed in body mass. PRT significantly increased insulin sensitivity by 46.3% (from 2.0 ± 1.2 to 2.8 ± 1.6 · 104 · min−1 · μU−1 · ml−1, P < 0.01), whereas it significantly decreased (−7.1%, P < 0.05) fasting blood glucose (from 146.6 ± 28.3 to 135.0 ± 29.3 mg/dl). Finally, a 15.5% increase in energy intake (from 2,287.1 ± 354.7 to 2,619.0 ± 472.1 kcal/day, P < 0.05) was observed.

CONCLUSIONS—Two sessions per week of PRT, without a concomitant weight loss diet, significantly improves insulin sensitivity and fasting glycemia and decreases abdominal fat in older men with type 2 diabetes.
A Prospective Study on the Prevalence of Metabolic Syndrome Among Healthy French Families
Authors: Maumus Sandy , Marie Bérangère , Siest Gérard , Visvikis-Siest Sophie
Published: March 2007

OBJECTIVE—The purpose of this study was to estimate the longitudinal variation of prevalence of metabolic syndrome within French families and to observe biological parameters involved in cardiovascular disease among their offspring.

RESEARCH DESIGN AND METHODS—Three hundred seventy-one apparently healthy families (1,366 individuals) taken from the STANISLAS cohort were studied. The subjects were examined at two time points with a 5-year interval (t0 and t+5). The crude prevalence of metabolic syndrome was assessed among parents according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP) definition.

RESULTS—The prevalence of metabolic syndrome was 5.9% in men and 2.1% in women at t0, rising to 7.2 and 5.4% in men and women, respectively, at t+5. Children of parents having metabolic syndrome showed higher levels of tumor necrosis factor-α (TNF-α), whereas their HDL cholesterol and apolipoprotein (apo) E concentrations were lower compared with those of age- and sex-matched control subjects (P ≤ 0.05). When applying NCEP ATP definitions that included either antihypertensive drugs only or all the drugs involved in metabolic syndrome, we found that the three parameters shared by the three different versions of the definition were TNF-α, HDL cholesterol, and an interaction between alcohol consumption and parental metabolic syndrome on HDL cholesterol concentration.

CONCLUSIONS—Metabolic syndrome increases with age in supposedly healthy families from the STANISLAS cohort. In offspring of affected people, it seems to be predictive of higher values of TNF-α and low HDL cholesterol levels, which are two major cardiovascular factors. Therefore, in terms of prevention, it is important to identify and follow subjects with metabolic syndrome as well as their offspring, even in apparently healthy populations, to enable early disease management.
Can Adoption of Regular Exercise Later in Life Prevent Metabolic Risk for Cardiovascular Disease?
Authors: Petrella Robert John , Lattanzio Chastity Nina , Demeray Amy , Varallo Vincent , Blore Rachel
Published: March 2007

OBJECTIVE—To determine the impact of chronic exercise training initiated later in life upon development of metabolic markers of cardiovascular disease risk.

RESEARCH DESIGN AND METHODS—Two inception cohorts of previously sedentary healthy adults aged 55–75 years at baseline (1989), one initiating regular supervised physical exercise training and the other a geographical similar sedentary control, were assessed for anthropometric, biochemical, and clinical markers of the metabolic syndrome and comorbidity over 10 years.

RESULTS—At baseline, active individuals aged 68 years compared with sedentary individuals aged 67 years had similar fitness levels (5.7 vs. 5.8 metabolic equivalents). At follow-up, complete data were obtained for 161 active and 136 sedentary subjects. Drop out occurred primarily because of failure to adhere to the exercise regimen and poor physical health for active and sedentary individuals, respectively. More metabolic abnormalities were seen in the sedentary group than in the active group for one or two (64 vs. 36%, P < 0.001) and three or more (35 vs. 22%, P < 0.003) abnormalities, respectively. In those assessed at follow-up, the sedentary group compared with the active group had lower fitness levels (5.0 [13.8% decrease] vs. 5.9 [3.5% increase] metabolic equivalents), had a greater likelihood of a positive exercise electrocardiogram or symptom (32 vs. 10%, P < 0.001), and had more comorbid conditions (Charlson Comorbidity Index score 0.9 vs. 0.4, P < 0.01).

CONCLUSIONS—Higher fitness achieved over 10 years of regular exercise training in older adults was associated with reduced development of metabolic risk factors for cardiovascular disease, fewer exercise-induced cardiac abnormalities, and reduced comorbidity.
Effect of Sibutramine on Weight Management and Metabolic Control in Type 2 Diabetes
Authors: Vettor Roberto , Serra Roberto , Fabris Roberto , Pagano Claudio , Federspil Giovanni
Published: March 2007

OBJECTIVE—The aim of this study was to provide a comprehensive meta-analysis of randomized controlled clinical studies on the effects of sibutramine on weight loss and glycemic control in obese subjects with type 2 diabetes.

RESEARCH DESIGN AND METHODS—Controlled clinical trials assessing the effect sizes of sibutramine on weight loss effects on glycemia in obese subjects with type 2 diabetes were identified and reviewed using the Cochrane Library, Medline, EMBASE, and a manual search.

RESULTS—Eight placebo-controlled, double-blind, randomized trials of sibutramine were included. After sibutramine treatment, the decrease in body weight and waist circumference was significantly greater than in the placebo group. Fasting blood glucose and HbA1c significantly decreased after sibutramine treatment. Treatment benefits were seen in plasma triglycerides and HDL, without significant variations in serum total and LDL cholesterol. No differences in systolic blood pressure between the sibutramine and the placebo groups were seen, while recording of diastolic blood pressure and heart rate showed that sibutramine produced a small increase relative to placebo.

CONCLUSIONS—A pharmacological approach in a weight management program for patients with type 2 diabetes may be helpful in glycemic control and in the management of other risk factors. Sibutramine may help improve glucose control because it is conducive to weight loss. The reviewed data on the effect of sibutramine further enforce the recommendations that weight management may be the most important therapeutic task for most obese subjects with type 2 diabetes.
Eliminating Inpatient Sliding-Scale Insulin
Authors: Baldwin David , Villanueva Griselda , McNutt Robert , Bhatnagar Sarika
Published: March 2007

OBJECTIVE—We studied a systematic program to reeducate our medical house officers on how to manage inpatient hyperglycemia without the use of sliding-scale insulin (SSI).

RESEARCH DESIGN AND METHODS—Patients admitted to the general medical service with diabetes or a blood glucose >140 mg/dl were included. HbA1c was measured in all patients, and therapy was modified if the HbA1c was >7.0%. For each 24 h on call, two house officers were responsible for all glucose management for their team’s patients and rounded with a teaching endocrinologist twice daily for 2 weeks. Oral agent or insulin therapy was modified using blood glucoses and HbA1c. All patients who required insulin therapy were treated with basal and bolus insulin, usually NPH and regular, adjusted twice daily.

RESULTS—During 8 weeks, 88 patients were identified and 16 house officers were instructed. The mean duration of diabetes was 10.4 years. Mean HbA1c level was 8.7%, and 48% of patients had HbA1c >8%. All patients with HbA1c >7% had diabetes therapy intensified. Overall 80% had their diabetes therapy changed by discharge. Compared with 98 historical control subjects, significantly fewer study patients had episodes of hyperglycemia, and a subgroup followed for 12 months showed a decrease in HbA1c from 10.1 to 8%.

CONCLUSIONS—Medical history, blood glucose, and HbA1c testing can effectively identify patients with inpatient hyperglycemia. Using direct ward-based teaching and a widely disseminated pocket set of guidelines, house officers can be taught to effectively and safely manage inpatient hyperglycemia without the use of SSI.
End-Stage Renal Disease due to Diabetes Among Southwestern American Indians, 1990–2001
Authors: Burrows Nilka Ríos , Narva Andrew S. , Geiss Linda S. , Engelgau Michael M. , Acton Kelly J.
Published: March 2007

OBJECTIVE—This study assesses trends in the incidence of diabetes-related end-stage renal disease (ESRD) among southwestern American Indians (SWAIs).

RESEARCH DESIGN AND METHODS—Using the U.S. Renal Data System, we obtained the total number of new cases of treated ESRD in which diabetes was the primary cause of renal failure in 1990 through 2001. The incidence of diabetes-related ESRD was calculated using census population figures and estimates of the SWAI population with diabetes, then age-adjusted to the 2000 U.S. population.

RESULTS—Between 1990 and 2001, the annual number of new patients starting treatment for diabetes-related ESRD in the SWAI total population increased from 154 to 320, and the age-adjusted diabetes-related ESRD incidence per 10,000 population increased 34% (6.2–8.3 per 10,000 people). However, after adjusting for the increasing number of people with diabetes in the SWAI population between 1993 and 2001, the age-adjusted incidence of diabetes-related ESRD among SWAIs with diabetes decreased 31%, from 80.4 to 55.8 per 10,000 people with diabetes. It decreased for both sexes and in all age-groups.

CONCLUSIONS—The increasing incidence of diabetes-related ESRD in the SWAI population parallels the growing prevalence of diabetes. However, since 1993 diabetes-related ESRD incidence decreased in the SWAI population with diabetes, consistent with national trends. This may reflect the reduction in risk factors and improvements in diabetes care practices in Indian communities.
Effect of a Peroxisome Proliferator–Activated Receptor-γ Agonist on Myocardial Blood Flow in Type 2 Diabetes
Authors: McMahon Graham T. , Plutzky Jorge , Daher Edouard , Bhattacharyya Tammy , Grunberger George , DiCarli Marcelo F.
Published: March 2007

OBJECTIVE—The relationship between coronary endothelial function and insulin resistance remains speculative. We sought to determine whether pioglitazone, an insulin-sensitizing peroxisome proliferator–activated receptor (PPAR)-γ agonist, improves cardiac endothelial function in individuals with type 2 diabetes.

RESEARCH DESIGN AND METHODS—Sixteen subjects with insulin-treated type 2 diabetes and without overt cardiovascular disease were randomly assigned to receive either 45 mg of pioglitazone or matching placebo for 3 months. Rest and adenosine-stimulated myocardial blood flow (MBF) were quantified with [13N]ammonia and positron emission tomography at baseline and study conclusion.

RESULTS—After 3 months, HbA1c levels dropped by 0.68% in the pioglitazone group and increased by 0.17% in the placebo group (P = 0.009 for difference between groups). Triglyceride (−93 vs. −39 mg/dl, P = 0.026) and HDL concentrations (+4.8 vs. −6.0 mg/dl, P = 0.014) improved significantly in the pioglitazone group compared with placebo. Despite these favorable changes, there was no demonstrable change in baseline MBF (−0.05 ± 0.24 vs. −0.09 ± 0.24 ml · min−1 · g−1, P = 0.45), adenosine-stimulated MBF (0.10 ± 0.75 vs. 0.14 ± 0.31 ml · min−1 · g−1, P = 0.25), or coronary flow reserve (0.45 ± 1.22 vs. 0.35 ± 0.72 ml · min−1 · g−1, P = 0.64) after 12 weeks of exposure to pioglitazone or placebo, respectively. Regression analysis revealed that lower glucose concentration at the time of the study was associated with higher coronary flow reserve (P = 0.012).

CONCLUSIONS—Pioglitazone treatment for 12 weeks in subjects with insulin-requiring type 2 diabetes had no demonstrable effect on coronary flow reserve despite metabolic improvements. Higher ambient glucose levels contribute to impaired vascular reactivity in individuals with diabetes.
Is the Diagnosis of Metabolic Syndrome Useful for Predicting Cardiovascular Disease in Asian Diabetic Patients?
Authors: Sone Hirohito , Mizuno Sachiko , Fujii Hitomi , Yoshimura Yukio , Yamasaki Yoshimitsu , Ishibashi Shun , Katayama Shigehiro , Saito Yasushi , Ito Hideki , Ohashi Yasuo , Akanuma Yasuo , Yamada Nobuhiro ,   the Japan Diabetes Complications Study Group
Published: March 2007

OBJECTIVE—The metabolic syndrome (MetS) is believed to be associated with an increased risk of cardiovascular disease (CVD). Although its prevalence is extremely high among diabetic patients, its prevalence in those with no history of CVD has not been determined. Moreover, prospective studies published on the association between MetS and cardiovascular events in diabetic populations have used only the World Health Organization (WHO) definition of MetS and included only white European subjects. The aim of this study was to determine the prevalence of MetS, as defined by both the WHO and the National Cholesterol Education Program (NCEP), and its predictive value for CVD in Asian diabetic patients in a long-term, prospective setting.

RESEARCH DESIGN AND METHODS—The baseline characteristics and incidence/hazard ratio of cardiovascular events (coronary heart disease and stroke) were determined in 1,424 Japanese type 2 diabetic patients with and without MetS, as defined by WHO (WHO-MetS) or the NCEP.

RESULTS—A high prevalence (38–53%, depending on sex and definition) of MetS was found among diabetic patients, even those with no history of CVD. During the 8-year study period, only WHO-MetS was a predictor for CVD in female patients. In male patients, although both definitions of MetS were significant predictors for CVD, individual components of MetS, such as hyperlipidemia or hypertension, were equivalent or better predictors.

CONCLUSIONS—We found that MetS is relatively common in diabetic patients with no history of CVD. We suggest that the commonly used definitions of MetS, at least in their present forms, have limited clinical usefulness for Asian diabetic patients and may need some ethnic group−specific modifications for global use.