bluuebunny/crossref_metadata_2025 huggingface dataset:
Prospective Association Between Lung Function and the Incidence of Diabetes
Authors: Ford Earl S. , Mannino David M.
Published: March 2007

OBJECTIVE—To determine whether impaired pulmonary function is a significant predictor of the incidence of diabetes.

RESEARCH DESIGN AND METHODS—Using data from the National Health and Nutrition Examination Survey Epidemiologic Follow-Up Study, a cohort study of a representative sample of U.S. adults, we examined the prospective associations between pulmonary function and incidence of diabetes. Our analyses included 4,830 U.S. men and women aged 25–74 years who had a baseline interview and examination (including spirometry) from 1971 through 1975 and were followed through 1992–1993. Incident diabetes (n = 443) was based on self- or proxy reports, hospitalization, or death certificates.

RESULTS—After multiple adjustment, forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), percentage of predicted FEV1, and percentage of predicted FVC were significantly and inversely associated with the incidence of diabetes, but the ratio of FEV1 to FVC was not. Obstructive lung disease (defined by the Global Initiative for Chronic Obstructive Lung Disease classification) was not significantly associated with the incidence of diabetes, but restrictive lung disease was (hazard ratio = 1.45, 95% CI 1.04–2.03). The association did not differ significantly by smoking status.

CONCLUSIONS—Although several prospective studies have found that impaired pulmonary function may increase the risk for developing diabetes, additional research is needed to better understand these relationships and their possible implications.
Treatment of Type 2 Diabetes in Childhood Using a Very-Low-Calorie Diet
Authors: Willi Steven M. , Martin Kelley , Datko Farrah M. , Brant Bethany P.
Published: March 2007

OBJECTIVE—Pharmacologic agents currently approved for use in children with type 2 diabetes (metformin and insulin) are less than optimal for some patients. We evaluated the use of a ketogenic, very-low-calorie diet (VLCD) in the treatment of type 2 diabetes.

RESEARCH DESIGN AND METHODS—We conducted a chart review of 20 children (mean age 14.5 ± 0.4 years) who consumed a ketogenic VLCD in the treatment of type 2 diabetes. Several response variables (BMI, blood pressure, HbA1c, blood glucose, and treatment regimens) were examined before, during, and up to 2 years after the diet and compared with a matched diabetic control group.

RESULTS—Before starting the diet, 11 of 20 patients were treated with insulin and 6 with metformin. Mean daily blood glucose values fell from 8.9 ± 1.1 to 5.5 ± 0.38 mmol/l (P < 0.0001) in the first 3 days of the VLCD, allowing insulin and oral agents to be discontinued in all but one subject. BMI fell from 43.5 ± 1.8 to 39.3 ± 1.8 kg/m2 (P < 0.0001) and HbA1c dropped from 8.8 ± 0.6 to 7.4 ± 0.6% (P < 0.005) as the diet was continued for a mean of 60 ± 8 days (range 4–130 days), and none required resumption of antidiabetic medications. Sustained decreases in BMI and insulin requirements were observed in patients remaining on the VLCD for at least 6 weeks when compared with those of the control group.

CONCLUSIONS—The ketogenic VLCD is an effective short-term, and possibly long-term, therapy for pediatric patients with type 2 diabetes. Blood glucose control and BMI improve, allowing the discontinuation of exogenous insulin and other antidiabetic agents. This diet, although strict, has potential as an alternative to pharmacologic therapies for this emerging subset of diabetic individuals.
Health-Related Quality of Life and Metabolic Control in Children With Type 1 Diabetes
Authors: Hesketh Kylie D. , Wake Melissa A. , Cameron Fergus J.
Published: March 2007

OBJECTIVE—To assess change in health-related quality of life (HRQOL) in children with diabetes over 2 years and determine its relationship to change in metabolic control.

RESEARCH DESIGN AND METHODS—In 1998, parents of children aged 5–18 years attending a tertiary diabetes clinic reported their child’s HRQOL using the Child Health Questionnaire PF-50. Those aged 12–18 years also self-reported their HRQOL using the analogous Child Health Questionnaire CF-80. HbA1c levels were recorded. In 2000, identical measures were collected for those who were aged ≤18 years and still attending the clinic.

RESULTS—Of 117 eligible subjects, 83 (71%) participated. Parents reported no significant difference in children’s HRQOL at baseline and follow-up. However, adolescents reported significant improvements on the Family Activities (P < 0.001), Bodily Pain (P = 0.04), and General Health Perceptions (P = 0.001) scales and worsening on the Behavior (P = 0.04) scale. HbA1c at baseline and follow-up were strongly correlated (r = 0.57). HbA1c increased significantly (mean 7.8% in 1998 vs. 8.5% in 2000; P < 0.001), with lower baseline HbA1c strongly predicting an increase in HbA1c over the 2 years (r2 = 0.25, P < 0.001). Lower parent-reported Physical Summary and adolescent-reported Physical Functioning scores at baseline also predicted increasing HbA1c. Poorer parent-reported Psychosocial Summary scores were related to higher HbA1c at both times but did not predict change in HbA1c.

CONCLUSIONS—Changes in parent and adolescent reports of HRQOL differ. Better physical functioning may protect against deteriorating HbA1c, at least in the medium term. While the HRQOL of children with diabetes does not appear to deteriorate over time, we should not be complacent, as it is consistently poorer than that of their healthy peers.
Fasting Intact Proinsulin Is a Highly Specific Predictor of Insulin Resistance in Type 2 Diabetes
Authors: Pfützner Andreas , Kunt Thomas , Hohberg Cloth , Mondok Agnes , Pahler Sabine , Konrad Thomas , Lübben Georg , Forst Thomas
Published: March 2007

OBJECTIVE—In later stages of type 2 diabetes, proinsulin and proinsulin-like molecules are secreted in increasing amounts with insulin. A recently introduced chemiluminescence assay is able to detect the uncleaved “intact” proinsulin and differentiate it from proinsulin-like molecules. This investigation explored the predictive value of intact proinsulin as an insulin resistance marker.

RESEARCH DESIGN AND METHODS—In total, 48 patients with type 2 diabetes (20 women and 28 men, aged 60 ± 9 years [means ± SD], diabetes duration 5.1 ± 3.8 years, BMI 31.2 ± 4.8 kg/m2, and HbA1c 6.9 ± 1.2%) were studied by means of an intravenous glucose tolerance test and determination of fasting values of intact proinsulin, insulin, resistin, adiponectin, and glucose. Insulin resistance was determined by means of minimal model analysis (MMA) (as the gold standard) and homeostatis model assessment (HOMA).

RESULTS—There was a significant correlation between intact proinsulin values and insulin resistance (MMA P < 0.05 and HOMA P < 0.01). Elevation of intact proinsulin values above the reference range (>10 pmmol/l) showed a very high specificity (MMA 100% and HOMA 92.9%) and a moderate sensitivity (MMA 48.6% and HOMA 47.1%) as marker for insulin resistance. Adiponectin values were slightly lower in the insulin resistant group, but no correlation to insulin resistance could be detected for resisitin in the cross-sectional design.

CONCLUSIONS—Elevated intact proinsulin seems to indicate an advanced stage of β-cell exhaustion and is a highly specific marker for insulin resistance. It might be used as arbitrary marker for the therapeutic decision between secretagogue, sensitizer, or insulin therapy in type 2 diabetes.
Accumulation of NH2-Terminal Fragment of Connective Tissue Growth Factor in the Vitreous of Patients With Proliferative Diabetic Retinopathy
Authors: Hinton David R. , Spee Christine , He Shikun , Weitz Stephen , Usinger William , LaBree Laurie , Oliver Noelynn , Lim Jennifer I.
Published: March 2007

OBJECTIVE—To evaluate the expression of connective tissue growth factor (CTGF) and its fragments in the vitreous of patients with proliferative diabetic retinopathy (PDR) and to localize CTGF expression in associated preretinal membranes.

RESEARCH DESIGN AND METHODS—Vitreous was obtained from 24 patients with active PDR, 4 patients with quiescent PDR, and 23 patients with other retinal diseases and no diabetes, including 5 patients with vitreous hemorrhage. Enzyme-linked immunosorbent assay was used to determine levels of whole CTGF and its NH2- and COOH-terminal fragments. Preretinal membranes from three patients with active PDR were stained immunohistochemically for the presence of CTGF and cell type-specific markers.

RESULTS—A significant increase in NH2-terminal CTGF fragment content was found in vitreous samples from patients with active PDR when compared with samples from nondiabetic patients (P < 0.0001) or patients with quiescent PDR (P = 0.02). Levels of NH2-terminal CTGF were also greater in vitreous samples from diabetic patients with vitreous hemorrhage compared with samples from nondiabetic patients with vitreous hemorrhage (P = 0.02). Vitreous levels of whole CTGF were similar in all groups. COOH-terminal fragments of CTGF were not detected. CTGF immunoreactivity was predominantly localized to smooth muscle actin-positive myofibroblasts within active PDR membranes.

CONCLUSIONS—NH2-terminal CTGF fragment content is increased in the vitreous of patients with active PDR, suggesting that it plays a pathogenic role or represents a surrogate marker of CTGF activity in the disorder. The localization of CTGF in myofibroblasts suggests a local paracrine mechanism for induction of fibrosis and neovascularization.
Diabetes and Oral Tumors in Hungary
Authors: Ujpál Márta , Matos Orsolya , Bíbok György , Somogyi Anikó , Szabó György , Suba Zsuzsanna
Published: March 2007

OBJECTIVE—Numerous publications have already demonstrated that diabetes is a risk factor for the development of periodontal diseases and various inflammatory lesions in the oral mucosa. A possible correlation between diabetes and oral premalignancies and tumors was examined in this study, as no literature data are available concerning this problem.

RESEARCH DESIGN AND METHODS—Stomato-oncological screening was carried out on 200 diabetic patients in the medical departments; the control group included 280 adult dentistry outpatients. The lesions found were classified into three groups: inflammatory lesions, benign tumors, and precancerous lesions. A retrospective diabetes screening of 610 inpatients with histologically confirmed oral malignancies was also performed. The control group comprised 574 complaint- and tumor-free adults. Fasting blood glucose levels were determined in both groups, and the tumor location was registered in the cancer patients.

RESULTS—Benign tumors were found in 14.5% and precancerous lesions in 8% of diabetic patients. In the control group these values were significantly lower, at 6.4 and 3.2%, respectively (P > 0.01). Earlier Hungarian screening studies indicated similar frequency of these lesions in the general population. The proportion of oral cavity lesions was higher among diabetic patients compared with that of the control patients. In the oral cancer patient group, diabetes was present in 14.6% and an elevated blood glucose level in 9.7%. These values are significantly higher than those for the tumor-free control group (P < 0.01). The gingival and labial tumor location was significantly more frequent among diabetic cancer patients than in the nondiabetic group (P < 0.01). The combination of diabetes and smoking means a higher risk for oral precancerous lesions and malignancies.

CONCLUSIONS—Diabetes may be a risk factor for oral premalignancies and tumors.
Cost Analysis of Human Islet Transplantation for the Treatment of Type 1 Diabetes in the Swiss-French Consortium GRAGIL
Authors: Guignard Adrienne P. , Oberholzer José , Benhamou Pierre-Yves , Touzet Sandrine , Bucher Pascal , Penfornis Alfred , Bayle François , Kessler Laurence , Thivolet Charles , Badet Lionel , Morel Philippe , Colin Cyril ,   On behalf of the GRAGIL Group
Published: March 2007

OBJECTIVE—To evaluate the cost of islet transplantation in type 1 diabetic patients with a functional renal graft in a multicenter network.

RESEARCH DESIGN AND METHODS—The study involved nine diabetic patients transplanted in the Swiss-French Groupe Rhône-Alpes, Rhin et Geneve pour la transplantation d’Ilots Langerhans (GRAGIL) consortium between March 1999 and June 2000. The direct medical costs were estimated from Social Security’s perspective from the inclusion of the patient to 1 year after transplantation. All cost components were computed separately and included evaluation, screening and candidacy, organ retrieval, islet processing, pancreas and islet transportation, hospitalization for transplantation, follow-up, medications (immunosuppressive, antidiabetic, and adjuvant drugs), and adverse events requiring hospitalization.

RESULTS—During the study period, 56 pancreata were processed and 14 islet preparations were transplanted. The average cost of an islet transplantation (procedure and 1-year follow-up) was €77,745 (French rate, year 2000). The four main cost components were islet preparation (30% of the total cost), adverse events (24%), drugs (14%), and hospitalization (13%).

CONCLUSIONS—Overall costs of islet transplantation are slightly higher than those of pancreas transplantation. The cell isolation process is a critical point; a reduction in overall cost will require more efficient ways of isolating high yields of viable islets. Costs generated by shipments within the GRAGIL network did not represent an economic burden. It can be expected that the costs will decrease with growing experience and improving technology.
l-Arginine-Induced Vasodilation of the Renal Vasculature Is Preserved in Uremic Type 1 Diabetic Patients After Kidney and Pancreas but not After Kidney-Alone Transplantation
Authors: De Cobelli Francesco , Fiorina Paolo , Perseghin Gianluca , Magnone Marta , Venturini Massimo , Zerbini Gianpaolo , Zanello Alessandro , Mazzolari Gabriella , Monti Lucilla , Di Carlo Valerio , Secchi Antonio , Del Maschio Alessandro
Published: March 2007

OBJECTIVE—In uremic type 1 diabetic patients, kidney and pancreas transplantation (KP) and kidney-alone transplantation (KD) provide full restoration of normal renal function; however, only KP, i.e., curing diabetes, is expected to prevent endothelial damages. Our aim was to study l-arginine-induced vasodilation of the renal vasculature in uremic type 1 diabetic patients after KP or KD using magnetic resonance (MR).

RESEARCH DESIGN AND METHODS—MR quantitative flow measurements were performed in 15 KP patients (mean age 39.0 ± 1.7 years, 10 men and 5 women), in 11 KD patients (mean age 47.3 ± 1.9 years, 7 men and 4 women), and in 8 nondiabetic kidney transplant patients (mean age 44.0 ± 4.8 years, 7 men and 1 woman), who were used as control subjects, to measure renal blood flow and velocity and renal vascular resistance before and immediately after infusion of l-arginine.

RESULTS—Renal blood flow and velocity were not different at baseline in KP, KD, and control subjects. In contrast, during l-arginine administration renal blood flow increased significantly in KP subjects (basal 8.4 ± 0.6 vs. post 9.6 ± 0.8 ml/s, Δ 14.3 ± 4.4%, P < 0.05) and in control subjects (basal 9.3 ± 0.8 vs. post 9.1 ± 0.8 ml/s, Δ 17.3 ± 6.2%, P < 0.01), while it remained unchanged in KD subjects (basal 10.0 ± 0.8 vs. post 11.6 ± 0.9 ml/s, Δ −1.36 ± 6.9%, NS). Parallel results have been achieved for renal blood velocity (KP subjects: 20.1 ± 4.9%, P < 0.01; control subjects: 23.0 ± 7.99%, P < 0.01; and KD subjects: −0.3 ± 6.5%; NS). A reduction in renal vascular resistance in response to l-arginine was evident in KP and control subjects but not in KD patients.

CONCLUSIONS—l-Arginine vasodilatory response was successfully assessed with MR quantitative flow measurements. KP patients and control subjects, but not those with KD, showed a preserved l-arginine-induced vasodilation of the renal vasculature.
Short-Term Intensive Insulin Therapy in Newly Diagnosed Type 2 Diabetes
Authors: Ryan Edmond A. , Imes Sharleen , Wallace Clarissa
Published: March 2007

OBJECTIVE—Type 2 diabetes is associated with defects in insulin secretion and insulin action. Hyperglycemia may aggravate these defects, a feature known as glucose toxicity. Previous studies have shown that acute correction of hyperglycemia in subjects with long-standing type 2 diabetes gives only short-term improvement in glycemic control after discontinuation of insulin. The current study attempts to identify any characteristics of patients with newly diagnosed type 2 diabetes (fasting glucose >11.0 mmol/l) who would have a long-term benefit, in terms of glycemic control, from a brief course of insulin therapy.

RESEARCH DESIGN AND METHODS—A total of 16 subjects (52 ± 2 years old [range 36–64], BMI 30.8 ± 1.9 kg/m2) with newly diagnosed type 2 diabetes had a 2–3 week course of intensive insulin therapy that was then discontinued.

RESULTS—Fasting glucose fell from 13.3 ± 0.7 to 7.0 ± 0.4 mmol/l, and this improvement was maintained at the 1-year follow-up (6.7 ± 0.3 mmol/l). The insulin area under the curve for the posttreatment oral glucose tolerance test also improved (8,251 ± 1,880 before therapy, 18,404 ± 4,040 directly after insulin therapy, and 42,368 ± 8,517 pmol · min at the 1-year follow-up). At 1 year, seven of the subjects maintained good glycemic control on diet therapy alone, eight required oral hypoglycemic agent (OHA) therapy, and one required insulin therapy. The distinguishing features of those who did not require OHA or insulin therapy were that they required less insulin during the active insulin therapy phase (0.37 ± 0.05 vs. 0.73 ± 0.07 units · kg−1 · day−1) and were able to attain a lower fasting serum glucose at the end of the period of insulin therapy (5.9 ± 0.3 vs. 7.7 ± 0.4 mmol/l).

CONCLUSIONS—These results demonstrate that in newly diagnosed type 2 diabetes with elevated fasting glucose levels, a 2- to 3-week course of intensive insulin therapy can successfully lay a foundation for prolonged good glycemic control. The ease with which normoglycemia is achieved on insulin may predict those patients who can later succeed in controlling glucose levels with attention to diet alone.
Diabetes, Depression, and Quality of Life
Authors: Goldney Robert D. , Phillips Pat J. , Fisher Laura J. , Wilson David H.
Published: March 2007

OBJECTIVE—The aim of the study was to assess the prevalence of diabetes and depression and their associations with quality of life using a representative population sample.

RESEARCH DESIGN AND METHODS—The study consisted of a representative population sample of individuals aged ≥15 years living in South Australia comprising 3,010 personal interviews conducted by trained health interviewers. The prevalence of depression in those suffering doctor-diagnosed diabetes and comparative effects of diabetic status and depression on quality-of-life dimensions were measured.

RESULTS—The prevalence of depression in the diabetic population was 24% compared with 17% in the nondiabetic population. Those with diabetes and depression experienced an impact with a large effect size on every dimension of the Short Form Health-Related Quality-of-Life Questionnaire (SF-36) as compared with those who suffered diabetes and who were not depressed. A supplementary analysis comparing both depressed diabetic and depressed nondiabetic groups showed there were statistically significant differences in the quality-of-life effects between the two depressed populations in the physical and mental component summaries of the SF-36.

CONCLUSIONS—Depression for those with diabetes is an important comorbidity that requires careful management because of its severe impact on quality of life.
Atorvastatin Decreases Apolipoprotein C-III in Apolipoprotein B-Containing Lipoprotein and HDL in Type 2 Diabetes
Authors: Dallinga-Thie Geesje M. , Berk-Planken Ingrid I.L. , Bootsma Aart H. , Jansen Hans ,   on behalf of the Diabetes Atorvastatin Lipid Intervention (DALI) Study Group
Published: March 2007

OBJECTIVE—Apolipoprotein (apo)C-III is a constituent of HDL (HDL apoC-III) and of apoB-containing lipoproteins (LpB:C-III). It slows the clearance of triglyceride-rich lipoproteins (TRLs) by inhibition of the activity of the enzyme lipoprotein lipase (LPL) and by interference with lipoprotein binding to cell-surface receptors. Elevated plasma LpB:C-III is an independent risk factor for cardiovascular disease. We studied the effect of atorvastatin on plasma LpB:C-III and HDL apoC-III.

RESEARCH DESIGN AND METHODS—We studied the effect of 30 weeks’ treatment with 10 and 80 mg atorvastatin on plasma apoC-III levels in a randomized, double-blind, placebo-controlled trial involving 217 patients with type 2 diabetes and fasting plasma triglycerides between 1.5 and 6.0 mmol/l.

RESULTS—Baseline levels of total plasma apoC-III, HDL apoC-III, and LpB:C-III were 41.5 ± 10.0, 17.7 ± 5.5, and 23.8 ± 7.7 mg/l, respectively. Plasma apoC-III was strongly correlated with plasma triglycerides (r = 0.74, P < 0.001). Atorvastatin 10- and 80-mg treatment significantly decreased plasma apoC-III (atorvastatin 10 mg, 21%, and 80 mg, 27%), HDL apoC-III (atorvastatin 10 mg, 22%, and 80 mg, 28%) and LpB:C-III (atorvastatin 10 mg, 23%, and 80 mg, 28%; all P < 0.001). The decrease in plasma apoC-III, mainly in LpB:C-III, strongly correlated with a decrease in triglycerides (atorvastatin 10 mg, r = 0.70, and 80 mg, r = 0.78; P < 0.001). Atorvastatin treatment also leads to a reduction in the HDL apoC-III-to-HDL cholesterol and HDL apoC-III-to-apoA-I ratios, indicating a change in the number of apoC-III per HDL particle (atorvastatin 10 mg, −21%, and 80 mg, −31%; P < 0.001).

CONCLUSIONS—Atorvastatin treatment resulted in a significant dose-dependent reduction in plasma apoC-III, HDL apoC-III, and LpB:C-III levels in patients with type 2 diabetes. These data indicate a potentially important antiatherogenic effect of statin treatment and may explain (part of) the triglyceride-lowering effect of atorvastatin.
Changes in Insulin Sensitivity in Response to Troglitazone Do Not Differ Between Subjects With and Without the Common, Functional Pro12Ala Peroxisome Proliferator–Activated Receptor-γ2 Gene Variant
Authors: Snitker Soren , Watanabe Richard M. , Ani Ifeanyi , Xiang Anny H. , Marroquin Aura , Ochoa Cesar , Goico Jose , Shuldiner Alan R. , Buchanan Thomas A.
Published: March 2007

OBJECTIVE—We have tested whether the Pro12Ala variant of the peroxisome proliferator–activated receptor (PPAR)-γ nuclear receptor involved in thiazolidinedione (TZD) action accounted for the failure of troglitazone to increase insulin sensitivity in nondiabetic Hispanic women with previous gestational diabetes treated in the Troglitazone in Prevention of Diabetes (TRIPOD) study.

RESEARCH DESIGN AND METHODS—Ninety-three women assigned to troglitazone had intravenous glucose tolerance tests at randomization and after 3 months of treatment with troglitazone, 400 mg/day, and were genotyped for the Pro12Ala variant of the PPAR-γ gene. Subjects were divided into tertiles based on their change in minimal model insulin sensitivity (Si) during the first 3 months of troglitazone treatment.

RESULTS—The mean changes in Si in the bottom, middle, and top tertiles of Si response were −0.21 ± 0.57, 0.91 ± 0.26, and 2.58 ± 1.32 min−1 per μU/ml · 10−4, respectively. Frequencies of the Ala/− genotype were 30, 22, and 26% in the same three tertiles (P = 0.77). Analysis of phenotypes by genotype revealed only small differences between the Pro/Pro and Ala/− groups, respectively, in baseline Si (2.76 ± 0.19 vs. 2.33 ± 0.33 × 10−4 min−1 per μU/ml; P = 0.27), the change in Si after 3 months of troglitazone treatment (1.19 ± 0.17 vs. 0.93 ± 0.30; P = 0.46), and the cumulative incidence of diabetes during a median follow-up of 30 months (13 vs. 17%; P = 0.66).

CONCLUSIONS—Among young Hispanic women at high risk for type 2 diabetes, the Pro12Ala variant of the PPAR-γ receptor gene did not explain the failure of ∼1/3 of subjects to increase their insulin sensitivity when placed on troglitazone at a dose of 400 mg/day.
Acute Alcohol Consumption Improves Insulin Action Without Affecting Insulin Secretion in Type 2 Diabetic Subjects
Authors: Avogaro Angelo , Watanabe Richard M. , Dall’Arche Alessandra , Vigili De Kreutzenberg Saula , Tiengo Antonio , Pacini Giovanni
Published: March 2007

OBJECTIVE—Long-term exposure to alcohol is associated with an improvement in insulin sensitivity. At this time, however, there is no definitive proof that alcohol per se has an effect on the insulin sensitivity index (Si) in type 2 diabetes patients. The aim of the present study was to assess the role of acute moderate alcohol intake on insulin sensitivity and insulin secretion in comparable subjects with and without type 2 diabetes.

RESEARCH DESIGN AND METHODS—Frequently sampled intravenous glucose tolerance tests (FSIGTs) were performed twice on eight healthy and eight type 2 diabetic volunteers. Forty grams of alcohol (vodka 40% wt/vol) or tap water were sipped from time −60 min to the end of the FSIGT.

RESULTS—Lactate area under the curve (AUC) was higher in both groups during the alcohol study than in the control study. Free fatty acid (FFA) AUC was higher in type 2 diabetic subjects than in control subjects; alcohol slightly reduced FFA by 17% in control subjects (34 ± 4 mmol · min−1 · l−1; P = 0.1) but significantly decreased FFA by 23% in type 2 diabetic subjects (54 ± 10; P = 0.007). β-Cell response was markedly reduced in type 2 diabetic subjects regardless of the type of study. Alcohol significantly increased Si in both groups.

CONCLUSIONS—Acute alcohol consumption improves insulin action without affecting β-cell secretion. This effect may be partly due to the inhibitory effect of alcohol on lipolysis. Alcohol intake increases insulin sensitivity and may partly explain both the J-shaped relationship between the prevalence of diabetes and the amount of alcohol consumption and the decreased mortality for myocardial infarction.
Serum γ-Glutamyltransferase and Risk of Metabolic Syndrome and Type 2 Diabetes in Middle-Aged Japanese Men
Authors: Nakanishi Noriyuki , Suzuki Kenji , Tatara Kozo
Published: March 2007

OBJECTIVE—To investigate the association between serum γ-glutamyltransferase (GGT) and risk of metabolic syndrome and type 2 diabetes in Japanese male office workers.

RESEARCH DESIGN AND METHODS—This study included 2,957 metabolic syndrome-free men and 3,260 nondiabetic men aged 35–59 years who did not have medication for hepatitis, alanine aminotransferase (ALT) levels higher than three times the upper limit of the reference range, or a history of cardiovascular disease at study entry. Subjects were reexamined at periodic annual health examinations over a 7-year period. We used a modified National Cholesterol Education Program definition of metabolic syndrome with BMI instead of waist circumference and the revised criteria of the American Diabetes Association for type 2 diabetes.

RESULTS—With adjustment for age, family history of diabetes, BMI, alcohol intake, cigarette smoking, regular physical activity (fasting plasma glucose for the risk of type 2 diabetes), and white blood cell (WBC) count, the risk of metabolic syndrome and type 2 diabetes increased in correlation with the levels of serum GGT, ALT, aspartate aminotransferase (AST), and alkaline phosphatase. Additional adjustment for all of the other liver enzymes attenuated these associations, but serum GGT remained a significant risk factor for the risk of both metabolic syndrome and type 2 diabetes (P for trend <0.001 for both). Top one-fifth versus bottom one-fifth relative risks of metabolic syndrome and type 2 diabetes were 2.23 (95% CI 1.51–3.30) and 2.44 (1.34–4.46), respectively.

CONCLUSIONS—These results indicate that serum GGT may be an important predictor for developing metabolic syndrome and type 2 diabetes in middle-aged Japanese men.
Insulin Resistance, Impaired Early Insulin Response, and Insulin Propeptides as Predictors of the Development of Type 2 Diabetes
Authors: Zethelius Björn , Hales C. Nicholas , Lithell Hans O. , Berne Christian
Published: March 2007

OBJECTIVE—Defects in insulin secretion and insulin action are the major abnormalities in the development of type 2 diabetes. In middle-aged subjects, elevated plasma proinsulin has been found to predict type 2 diabetes. Therefore, our aim was to study the longitudinal relationships between baseline determinations of insulin sensitivity index (Si) assessed by euglycemic insulin clamp, the early insulin response (EIR) at an oral glucose tolerance test (OGTT), fasting intact proinsulin, 32–33 split proinsulin and specific insulin, and the development of type 2 diabetes in a population-based cohort of 70-year-old nondiabetic men (n = 667) with 7-year follow-up.

RESEARCH DESIGN AND METHODS—A euglycemic insulin clamp study and a 75-g OGTT were performed at baseline, and fasting peptide concentrations were measured using specific two-site immunometric assays. Results from logistic regression models are presented as odds ratios (ORs) with 95% CIs for a 1-SD increase in the predictor variable.

RESULTS—In separate multivariate analyses adjusted for EIR (OR 0.72, 95% CI 0.59–0.89) and Si (0.68, 0.58–0.88), 32–33 split proinsulin (1.49, 1.18–1.88) or intact proinsulin (1.30, 1.04–1.63) were significantly associated with the development of type 2 diabetes, whereas specific insulin (1.24, 0.91–1.66) was not. The significant associations between 32–33 split or intact proinsulin and the development of type 2 diabetes were unaltered after adjustment for BMI and glucose tolerance.

CONCLUSIONS—Insulin propeptides predicted type 2 diabetes over a 7-year period in elderly men, independent of the EIR and Si.
Translating Lifestyle Intervention to Practice in Obese Patients With Type 2 Diabetes
Authors: Wolf Anne M. , Conaway Mark R. , Crowther Jayne Q. , Hazen Kristen Y. , L.Nadler Jerry , Oneida Beverly , Bovbjerg Viktor E.
Published: March 2007

OBJECTIVE—To assess the efficacy of a lifestyle intervention program that can be readily translated into clinical practice for obese patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS—The study consisted of a 12-month randomized controlled trial of 147 health plan members with type 2 diabetes and obesity (BMI ≥27 kg/m2). Participants were randomized to lifestyle case management or usual care. Case management entailed individual and group education, support, and referral by registered dietitians; intervention cost was $350 per person. Individuals treated with usual care received educational material. Both groups received ongoing primary care. Outcomes were difference between groups for change in weight (kilograms), waist circumference (centimeters), HbA1c, fasting lipid levels, use of prescription medications, and health-related quality of life.

RESULTS—Case management resulted in greater weight loss (P < 0.001), reduced waist circumference (P < 0.001), reduced HbA1c level (P = 0.02), less use of prescription medications (P = 0.03), and improved health-related quality of life (P < 0.001) compared with usual care. The 12-month group difference in weight loss and waist circumference was 3.0 kg (95% CI −5.4 to −0.6) and −4.2 cm (−6.8 to −1.6). HbA1c differences were greatest at 4 months (−0.59%, P = 0.006) but not significant by 12 months (−0.19%, P = 0.45). Participants in the case management group lowered their use of medications, primarily diabetes medications, by 0.8 medications per day more than participants treated with usual care (P = 0.03). In seven of nine quality-of-life domains, the case management group improved compared with usual care (P < 0.05).

CONCLUSIONS—Moderate-cost dietitian-led lifestyle case management may improve diverse health indicators among obese patients with type 2 diabetes.
Prevalence of Lower-Extremity Disease in the U.S. Adult Population ≥40 Years of Age With and Without Diabetes
Authors: Gregg Edward W. , Sorlie Paul , Paulose-Ram Ryne , Gu Qiuping , Eberhardt Mark S. , Wolz Michael , Burt Vicki , Curtin Lester , Engelgau Michael , Geiss Linda
Published: March 2007

OBJECTIVE—Although lower-extremity disease (LED), which includes lower-extremity peripheral arterial disease (PAD) and peripheral neuropathy (PN), is disabling and costly, no nationally representative estimates of its prevalence exist. The aim of this study was to examine the prevalence of lower-extremity PAD, PN, and overall LED in the overall U.S. population and among those with and without diagnosed diabetes.

RESEARCH DESIGN AND METHODS—The analysis consisted of data for 2,873 men and women aged ≥40 years, including 419 with diagnosed diabetes, from the 1999–2000 National Health and Nutrition Examination Survey. The main outcome measures consisted of the prevalence of lower-extremity PAD (defined as ankle-brachial index <0.9), PN (defined as ≥1 insensate area based on monofilament testing), and of any LED (defined as either PAD, PN, or history of foot ulcer or lower-extremity amputations).

RESULTS—Of the U.S. population aged ≥40 years, 4.5% (95% CI 3.4–5.6) have lower-extremity PAD, 14.8% (12.8–16.8) have PN, and 18.7% (15.9–21.4) have any LED. Prevalence of PAD, PN, and overall LED increases steeply with age and is higher (P < 0.05) in non-Hispanic blacks and Mexican Americans than non-Hispanic whites. The prevalence of LEDs is approximately twice as high for individuals with diagnosed diabetes (PAD 9.5% [5.5–13.4]; PN 28.5% [22.0–35.1]; any LED 30.2% [22.1–38.3]) as the overall population.

CONCLUSIONS—LED is common in the U.S. and twice as high among individuals with diagnosed diabetes. These conditions disproportionately affect the elderly, non-Hispanic blacks, and Mexican Americans.
Reduction of Cardiovascular Events by Simvastatin in Nondiabetic Coronary Heart Disease Patients With and Without the Metabolic Syndrome
Authors: Pyörälä Kalevi , Ballantyne Christie M. , Gumbiner Barry , Lee Michael W. , Shah Arvind , Davies Michael J. , Mitchel Yale B. , Pedersen Terje R. , Kjekshus John ,   for the Scandinavian Simvastatin Survival Study Group
Published: March 2007

OBJECTIVE—To assess the effect of simvastatin treatment on the risk of cardiovascular events in nondiabetic patients with coronary heart disease (CHD) with and without the metabolic syndrome, as defined by the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP-III).

RESEARCH DESIGN AND METHODS—Subgroup analyses were performed on data from 3,933 nondiabetic patients with clinically established CHD, serum total cholesterol level 5.5–8.0 mmol/l, and serum triglyceride level ≤2.5 mmol/l who were participating in the Scandinavian Simvastatin Survival Study (4S), a randomized, placebo-controlled trial. End points were total mortality, coronary mortality, major CHD event, myocardial revascularization, any CHD event, stroke, and any atherosclerotic event.

RESULTS—Over the 5.4-year median follow-up period, simvastatin produced similar changes in serum lipid levels in 893 patients with the metabolic syndrome and in 3,040 patients without the metabolic syndrome. The relative risks of main end points in simvastatin-treated patients compared with placebo-treated patients with the metabolic syndrome were as follows: total mortality 0.54 (95% CI 0.36–0.82), coronary mortality 0.39 (0.23–0.65), major CHD event 0.59 (0.45–0.77), and any atherosclerotic event 0.69 (0.56–0.84). The corresponding RRs in patients without the metabolic syndrome were 0.72 (0.56–0.91), 0.62 (0.45–0.84), 0.71 (0.61–0.82), and 0.76 (0.68–0.85).

CONCLUSIONS—Nondiabetic CHD patients with or without the metabolic syndrome realize from simvastatin treatment a similar, substantial relative reduction in the risk of cardiovascular events. The absolute benefit may be greater in patients with the metabolic syndrome because they are at a higher absolute risk.
Association of Carotid Intima-Media Thickness and Arterial Stiffness With Diabetic Retinopathy
Authors: Rema Mohan , Mohan Viswanathan , Deepa Raj , Ravikumar Radhakrishnan
Published: March 2007

OBJECTIVE—The aim of this study was to assess the association of intima-media thickness (IMT) and arterial stiffness with diabetic retinopathy in an Asian-Indian population that has very high prevalence rates of diabetes and coronary artery disease.

RESEARCH DESIGN AND METHODS—The study was conducted on 600 type 2 diabetic subjects randomly selected from the Chennai Urban Rural Epidemiology Study (CURES), which is an ongoing population-based study of a representative population of Chennai. When present, retinopathy was graded according to a modified Early Treatment Diabetic Retinopathy Study grading system. IMT was determined using high-resolution B-mode ultrasonography. Arterial stiffness was measured by assessing the augmentation index (AI) using the Sphygmocor apparatus.

RESULTS—Retinopathy was diagnosed in 116 of 590 (19.6%) subjects in whom retinal photography was possible. Mean values of IMT (0.93 ± 0.36 vs. 0.85 ± 0.21 mm, P = 0.001) and AI (27.9 ± 8.9 vs. 25.8 ± 9.6%, P = 0.031) were significantly higher among diabetic subjects with retinopathy compared with those without. Both IMT (P = 0.024) and AI (P = 0.050) showed a significant association to diabetic retinopathy, even after adjusting for age, duration of diabetes, HbA1c, serum cholesterol, serum triglycerides, and microalbuminuria.

CONCLUSIONS—Diabetic retinopathy is associated with IMT and AI, suggesting that common pathogenic mechanisms might predispose to diabetic micro- and macroangiopathy.
Approach to the Pathogenesis and Treatment of Nonalcoholic Steatohepatitis
Authors: Medina Jesús , Fernández-Salazar Luis I. , García-Buey Luisa , Moreno-Otero Ricardo
Published: March 2007

Nonalcoholic steatohepatitis (NASH) represents an advanced stage of fatty liver disease developed in the absence of alcohol abuse. Its increasing prevalence in western countries, the diagnostic difficulties by noninvasive tests, and the possibility of progression to advanced fibrosis and even cirrhosis make NASH a challenge for hepatologists. NASH is frequently associated with type 2 diabetes and the metabolic syndrome, and several genetic and acquired factors are involved in its pathogenesis. Insulin resistance plays a central role in the development of a steatotic liver, which becomes vulnerable to additional injuries. Several cyclic mechanisms leading to self-enhancement of insulin resistance and hepatic accumulation of fat have been recently identified. Excess intracellular fatty acids, oxidant stress, tumor necrosis factor-α, and mitochondrial dysfunction are causes of hepatocellular injury, thereby leading to disease progression and to the establishment of NASH. Intestinal bacterial overgrowth also plays a role, by increasing production of endogenous ethanol and proinflammatory cytokines. Therapeutic strategies aimed at modulating insulin resistance, normalizing lipoprotein metabolism, and downregulating inflammatory mediators with probiotics have promising potential.
Costs of Lower-Extremity Ulcers Among Patients With Diabetes
Authors: Stockl Karen , Vanderplas Ann , Tafesse Eskinder , Chang Eunice
Published: March 2007

OBJECTIVE—The objective of this study was to characterize health care costs associated with diabetic lower-extremity ulcers.

RESEARCH DESIGN AND METHODS—Adult patients with diabetes who had a lower-extremity ulcer episode during 2000 and 2001 were identified using claims data. Ulcer-related direct health care costs were computed for each episode. Episodes were stratified according to severity level based on the Wagner classification.

RESULTS—A total of 2,253 patients were identified. The mean age was 68.9 years, and 59% of the patients were male. The average episode duration was 87.3 ± 82.8 days. Total ulcer-related costs averaged $13,179 per episode and increased with severity level, ranging from $1,892 (level 1) to $27,721 (level 4/5). Inpatient hospital charges accounted for 77% ($10,188) of the overall cost, indicating that hospitalization was a major cost driver. Total ulcer-related costs were significantly higher for patients <65 years of age compared with those of older patients ($16,390 vs. $11,925, P = 0.02) and for patients with inadequate vascular status compared with patients with adequate vascular status ($23,372 vs. $5,218, P < 0.0001). Patients who progressed to a higher severity level also had significantly higher ulcer-related costs compared with patients who did not progress ($20,136 vs. $3,063, P < 0.0001).

CONCLUSIONS—The high costs of treating diabetic lower-extremity ulcers emphasize the value of intensive outpatient interventions designed to prevent ulcer progression.
Effect of Training Status on Regional Disposal of Circulating Free Fatty Acids in the Liver and Skeletal Muscle During Physiological Hyperinsulinemia
Authors: Iozzo Patricia , Takala Teemu , Oikonen Vesa , Bergman Jörgen , Grönroos Tove , Ferrannini Ele , Nuutila Pirjo , Knuuti Juhani
Published: March 2007

OBJECTIVE—Fat metabolism is increasingly implicated in the pathogenesis of type 2 diabetes. Endurance training has been shown to prevent hepatic steatosis and to alter skeletal muscle fat metabolism, and regional free fatty acid (FFA) uptake adaptations were suggested as a mechanism. Thus, we tested whether endurance training modifies the uptake of plasma FFAs occurring in the liver and in skeletal muscle during anabolic, i.e., hyperinsulinemic, conditions.

RESEARCH DESIGN AND METHODS—Trained and untrained healthy male subjects underwent positron emission tomography scanning of the liver and thigh regions, with the FFA analog 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid, during euglycemic hyperinsulinemia. Tracer influx rate constants in skeletal muscle (MKi) and liver (LKi) were multiplied by plasma FFA levels to obtain FFA uptake for skeletal muscle (MFU) and liver (LFU), respectively.

RESULTS—Athletes showed increased Vo2max (P < 0.0001), insulin-mediated glucose disposal (M value, 61 ± 4 vs. 46 ± 3 μmol · min−1 · kg−1, P = 0.01), and plasma lactate levels during the clamp and lower percentage of body fat mass (P = 0.002). MKi was 25% higher in athletes than in sedentary men (P = 0.03). In all subjects, MKi and MFU were positively correlated with the M value (r = 0.56, P = 0.02, and r = 0.51, P = 0.03, respectively) and with plasma lactate levels (r = 0.63, P = 0.006, and r = 0.63, P = 0.005, respectively). LKi was significantly reduced by 20% in the athletes (P = 0.04). By multiple regression, LFU was inversely correlated with the two fitness categories (P = 0.008), and it was lower in athletes. Linear fitting of liver data showed time consistency, indicating no release of FFAs as a mechanism for the reduced liver retention in athletes.

CONCLUSIONS—We conclude that endurance training promotes insulin-mediated glucose and FFA disposal in skeletal muscle, while lowering hepatic FFA uptake. Such changes may result in a divergent pattern of fat accumulation in the two organs.
Diabetes Research in the Department of Veterans Affairs
Authors: Reiber Gayle E. , Boyko Edward J.
Published: March 2007

OBJECTIVE—To provide an overview of the Department of Veterans Affairs (VA) research activities, highlighting diabetes-related research.

RESEARCH DESIGN AND METHODS—Diabetes is an important component of the VA research portfolio. All four VA research services support aspects of diabetes research. VA diabetes research projects and funding were examined from 1998 to 2003.

RESULTS—VA scientists are conducting research on diabetes genetics, etiology, diagnosis, therapy, epidemiology, health services, and rehabilitation. VA research funding is available to answer important veteran-relevant questions through peer review, Center of Excellence activities, and multisite trial mechanisms. Many VA scientists also receive research support from nonfederal sources, including private corporations and nonprofit foundations. The VA Office of Research and Development actively supports training the next generation of researchers through their career development awards and the VA health profession training programs.

CONCLUSIONS—The VA’s diabetes research portfolio is extensive and includes many investigators, trainees, and fellows. There is substantial leveraging of VA diabetes research with support from other federal and nonfederal funding agencies, foundations, and private corporations. VA diabetes research findings benefit the global diabetes care community.
A Two-Center Randomized Controlled Feasibility Trial of Insulin Pump Therapy in Young Children With Diabetes
Authors: Wilson Darrell M. , Buckingham Bruce A. , Kunselman Elizabeth L. , Sullivan Mary M. , Paguntalan Helen U. , Gitelman Stephen E.
Published: March 2007

OBJECTIVE—Our goals were to determine if continuous subcutaneous insulin infusion (CSII), compared with those continuing multiple daily injections (MDIs), can be safely used in young children, if those on CSII will have superior glycemic control, if subjects using CSII will have less hypoglycemia for their level of control, and if families using CSII will report an improved quality of life.

RESEARCH DESIGN AND METHODS—We conducted a randomized 1-year feasibility trial comparing CSII with continuing MDIs in preschool children with a history of type 1 diabetes for at least 6 months’ duration. Prospective outcomes included measures of overall glycemic control (HbA1c and continuous glucose monitoring system), the incidence of severe hypoglycemia and diabetic ketoacidosis, the percent of glucose values below 3.9 mmol/l, and the parents’ report of quality of life.

RESULTS—The 19 subjects’ ages ranged from 1.7 to 6.1 (mean 3.6) years, duration of diabetes ranged from 0.6 to 2.6 (mean 1.4) years, and baseline HbA1c ranged from 6.7 to 9.6% (mean 7.9%). Seven subjects were male. Nine subjects were randomized to start CSII and 10 to continue on MDI. All baseline characteristics were well balanced. Overall metabolic control, diabetes quality of life, and the incidence of hypoglycemia were similar in the two groups. No subject had diabetic ketoacidosis, while one subject in each group had an episode of severe hypoglycemia. No CSII subject discontinued using the pump during or after the study.

CONCLUSIONS—CSII can be a safe and effective method to deliver insulin in young children.
The Effect of Chronic Pain on Diabetes Patients’ Self-Management
Authors: Krein Sarah L. , Heisler Michele , Piette John D. , Makki Fatima , Kerr Eve A.
Published: March 2007

OBJECTIVE—Many adults experience chronic pain, yet little is known about the consequences of such pain among individuals with diabetes. The purpose of this study was to examine whether and how chronic pain affects diabetes self-management.

RESEARCH DESIGN AND METHODS—This is a cross-sectional study of 993 patients with diabetes receiving care through the Department of Veterans Affairs (VA). Data on chronic pain, defined as pain present most of the time for 6 months or more during the past year, and diabetes self-management were collected through a written survey. Multivariable regression techniques were used to examine the association between the presence and severity of chronic pain and difficulty with diabetes self-management, adjusting for sociodemographic and other health characteristics including depression.

RESULTS—Approximately 60% of respondents reported chronic pain. Patients with chronic pain had poorer diabetes self-management overall (P = 0.002) and more difficulty following a recommended exercise plan (adjusted odds ratio [OR] 3.0 [95% CI 2.1–4.1]) and eating plan (1.6 [1.2–2.1]). Individuals with severe or very severe pain, compared with mild or moderate, reported significantly poorer diabetes self-management (P = 0.003), including greater difficulty with taking diabetes medications (2.0 [1.2–3.4]) and exercise (2.5 [1.3–5.0]).

CONCLUSIONS—Chronic pain was prevalent in this cohort of patients with diabetes. Even after controlling for general health status and depressive symptoms, chronic pain was a major limiting factor in the performance of self-care behaviors that are important for minimizing diabetes-related complications. Competing demands, such as chronic pain, should be considered when working with patients to develop effective diabetes self-care regimens.