bluuebunny/crossref_metadata_2025 huggingface dataset:
Diabetic Peripheral Neuropathy and Depressive Symptoms
Authors: Vileikyte Loretta , Leventhal Howard , Gonzalez Jeffrey S. , Peyrot Mark , Rubin Richard R. , Ulbrecht Jan S. , Garrow Adam , Waterman Christine , Cavanagh Peter R. , Boulton Andrew J.M.
Published: March 2007

OBJECTIVE—We examined the association between severity of diabetic peripheral neuropathy and depressive symptoms and investigated the potential mediators of this association.

RESEARCH DESIGN AND METHODS—The Hospital Anxiety and Depression Scale (HADS) was used to assess depressive symptoms in 494 patients (mean age 62 years; 70% male; 72% type 2 diabetic) with diabetic neuropathy diagnosed by the Neuropathy Disability Score (NDS) and the Vibration Perception Threshold (VPT). Diabetic neuropathy symptoms, activities of daily living (ADLs), and social self-perception were measured by the neuropathy and foot ulcer–specific quality-of-life instrument, NeuroQoL; perceptions of diabetic neuropathy symptom unpredictability and the lack of effective treatment were assessed by the revised Illness Perception Questionnaire.

RESULTS—Both the NDS and VPT were significantly associated with the HADS after controlling for demographic and disease variables. Although diabetic neuropathy symptoms mediated this association, with unsteadiness being most strongly associated with HADS, the relationship between foot ulceration and depression was nonsignificant. The association between diabetic neuropathy symptoms and HADS was partially mediated by two sets of psychosocial variables: 1) perceptions of diabetic neuropathy symptom unpredictability and the lack of treatment control and 2) restrictions in ADLs and changes in social self-perception.

CONCLUSIONS—These findings establish the association between diabetic neuropathy and depressive symptoms and identify potential targets for interventions to alleviate depressive symptoms in persons affected by diabetic peripheral neuropathy.
Mortality in Childhood-Onset Type 1 Diabetes
Authors: Dahlquist Gisela , Källén Bengt
Published: March 2007

OBJECTIVE—To describe the age- and sex-specific mortality in a cohort of young type 1 diabetic patients and to analyze the causes of death with special focus on suicide, accidents, and unexplained deaths.

RESEARCH DESIGN AND METHODS—A population-based incident childhood diabetes register, covering onset cases since 1 July 1977, was linked to the Swedish Cause of Death Register up to 31 December 2000. The official Swedish population register was used to calculate age- and sex-standardized mortality rates (SMRs), excluding neonatal deaths. To analyze excess risks for specific diagnoses, case subjects were compared with five nondiabetic control subjects, matched by age, sex, and year of death. Death certificates were collected for all case and control subjects. For case subjects with an unclear diagnosis, hospital records and/or forensic autopsy reports were obtained.

RESULTS—Mean age- and sex-SMR was 2.15 (95% CI 1.70–2.68) and tended to be higher among females (2.65 vs. 1.93, P = 0.045). Mean age at death was 15.2 years (range 1.2–27.3) and mean duration 8.2 years (0–20.7). Twenty-three deaths were clearly related to diabetes; 20 died of diabetic ketoacidosis. Only two case subjects died with late diabetes complications (acute coronary infarction). Thirty-three case subjects died with a diagnosis not directly related to diabetes; 7 of them committed suicide, and 14 died from accidents. There was no significant difference in traffic accidents (odds ratio 1.02 [95% CI 0.40–2.37]). Obvious suicide tended to be increased but not statistically significantly so (1.55 [0.54–3.89]). Seventeen diabetic case subjects were found deceased in bed without any cause of death found at forensic autopsy. Only two of the control subjects died of similar unexplained deaths.

CONCLUSIONS—In a well-developed health care system, there is still a significant excess mortality in young type 1 diabetic patients. We confirm a very large proportion of unexplained deaths in bed, which should be further studied. There is no clear excess death rate caused by suicide or traffic accidents among young diabetic subjects.
Validation of Insulin Resistance Indexes in a Stable Renal Transplant Population
Authors: Oterdoom Leendert H. , de Vries Aiko P.J. , van Son Willem J. , van der Heide Jaap J. Homan , Ploeg Rutger J. , Gansevoort Ron T. , de Jong Paul E. , Gans Rijk O.B. , Bakker Stephan J.L.
Published: March 2007

OBJECTIVE—The purpose of this study was to investigate the validity of established insulin resistance indexes, based on fasting blood parameters, in a stable renal transplant population.

RESEARCH DESIGN AND METHODS—Fasting insulin, homeostasis model assessment (HOMA), the quantitative insulin sensitivity check index (QUICKI), and McAuley’s index were assessed for correlation and agreement with whole-body glucose uptake (M value) divided by prevailing serum insulin concentrations (I value) assessed during a hyperinsulinemic-euglycemic clamp in 51 stable renal transplant recipients, who were at a median of 7.5 years after transplant. Multivariate linear regression analyses were used to determine independent risk factors for insulin resistance.

RESULTS—The M/I value correlated with fasting insulin concentration (r = −0.56), HOMA (r = −0.53), QUICKI (r = 0.52), and McAuley’s index (r = 0.61) (all P < 0.01). Linear regression showed agreement between all indexes and insulin resistance. However, McAuley’s index showed the strongest agreement irrespective of age, sex, renal allograft function, and obesity. In multivariate analysis, fasting insulin concentration (β = −0.59, P = 0.002), fasting triglyceride concentration (β = −0.33, P = 0.04), and BMI (β = −1.22, P = 0.05) were independently associated with the M/I value.

CONCLUSIONS—All investigated insulin resistance indexes were valid estimates of insulin resistance in the long-term stable renal transplant population. However, correlation and agreement were strongest for McAuley’s index. In addition to fasting insulin and triglyceride concentrations, of which McAuley’s index is composed, only BMI seemed to be independently associated with insulin resistance in this population.
A Prevalent Amino Acid Polymorphism at Codon 98 (Ala98Val) of the Hepatocyte Nuclear Factor-1α Is Associated With Maturity-Onset Diabetes of the Young and Younger Age at Onset of Type 2 Diabetes in Asian Indians
Authors: Anuradha Shekher , Radha Venkatesan , Deepa Raj , Hansen Torben , Carstensen Bendix , Pedersen Oluf , Mohan Viswanathan
Published: March 2007

OBJECTIVE—Among Europeans, mutations in the hepatocyte nuclear factor-1α (HNF1α) gene are associated with the most common form of maturity-onset diabetes of the young (MODY)3. In Asian Indians, type 2 diabetes occurs earlier and often overlaps with MODY, but the genetics of the latter are unknown. The aim of this study was to estimate the prevalence of Ala98Val polymorphism of the HNF1α gene in different types of diabetes in Asian Indians.

RESEARCH DESIGN AND METHODS—Genotyping of Ala98Val was done by the PCR–restriction fragment–length polymorphism method in the following groups: 1) MODY, defined as non–insulin-dependent diabetes (age at onset <25 years) and vertical transmission of diabetes through at least three generations (n = 122); 2) very-early-onset type 2 diabetes (age at onset <25 years) without family history (n = 23); 3) early-onset type 2 diabetes (age at onset between 26 and 40 years, n = 171); 4) late-onset type 2 diabetes (age at onset >40 years, n = 133); 5) type 1 diabetes (n = 150); and 6) normal glucose tolerance (n = 130). The frequency of the Val genotypes was compared in the diabetic and control groups.

RESULTS—The frequency of the Val allele was significantly higher in MODY patients (P = 0.0013) compared with control groups. Furthermore, in the total group of patients with type 2–like diabetes (groups 1–4), the Val allele was associated with an earlier diagnosis of diabetes (P = 0.0002).

CONCLUSIONS—Among Asian Indians, the Ala98Val polymorphism of HNF1α gene is associated with MODY and with earlier age at onset of type 2 diabetes.
The Influence of Age, Duration of Diabetes, Cataract, and Pupil Size on Image Quality in Digital Photographic Retinal Screening
Authors: Scanlon Peter Henry , Foy Chris , Malhotra Raman , Aldington Stephen J.
Published: March 2007

OBJECTIVE—To evaluate the effect of age, duration of diabetes, cataract, and pupil size on the image quality in digital photographic screening.

RESEARCH DESIGN AND METHODS—Randomized groups of 3,650 patients had one-field, nonmydriatic, 45° digital retinal imaging photography before mydriatic two-field photography. A total of 1,549 patients were then examined by an experienced ophthalmologist. Outcome measures were ungradable image rates, age, duration of diabetes, detection of referable diabetic retinopathy, presence of early or obvious central cataract, pupil diameter, and iris color.

RESULTS—The ungradable image rate for nonmydriatic photography was 19.7% (95% CI 18.4–21.0) and for mydriatic photography was 3.7% (3.1–4.3). The odds of having one eye ungradable increased by 2.6% (1.6–3.7) for each extra year since diagnosis for nonmydriatic, by 4.1% (2.7–5.7) for mydriatic photography irrespective of age, by 5.8% (5.0–6.7) for nonmydriatic, and by 8.4% (6.5–10.4) for mydriatic photography for every extra year of age, irrespective of years since diagnosis. Obvious central cataract was present in 57% of ungradable mydriatic photographs, early cataract in 21%, no cataract in 9%, and 13% had other pathologies. The pupil diameter in the ungradable eyes showed a significant trend (P < 0.001) in the three groups (obvious cataract 4.434, early cataract 3.379, and no cataract 2.750).

CONCLUSIONS—The strongest predictor of ungradable image rates, both for nonmydriatic and mydriatic digital photography, is the age of the person with diabetes. The most common cause of ungradable images was obvious central cataract.
The Prevalence of the Metabolic Syndrome Did Not Increase in Mexico City Between 1990–1992 and 1997–1999 Despite More Central Obesity
Authors: Lorenzo Carlos , Williams Ken , Gonzalez-Villalpando Clicerio , Haffner Steven M.
Published: March 2007

OBJECTIVE—Trends in the metabolic syndrome might follow trends in obesity. We examined this hypothesis in the Mexico City Diabetes Study (MCDS), a study that showed rising trends in obesity, and the effect of the metabolic syndrome on the risk of coronary heart disease (CHD).

RESEARCH DESIGN AND METHODS—Designed as a population-based study, the MCDS enrolled subjects in 1990–1992 (n = 2,282). Follow-up visits were held in 1993–1995 (n = 1,764) and 1997–1999 (n = 1,754). We used the revised metabolic syndrome definition of the National Cholesterol Education Program and the Framingham equations to estimate the 10-year CHD risk.

RESULTS—In men, the age-adjusted prevalence of the metabolic syndrome was 38.9% in 1990–1992, 43.4% in 1993–1995, and 39.9% in 1997–1999; in women, the prevalences were 65.4, 65.7, and 59.9%, respectively. The prevalence did not change in men (P = 0.349) between 1990–1992 and 1997–1999, but decreased in women (P < 0.001). A prevalence increase was demonstrated for elevated waist circumference (men, P < 0.001; women, P < 0.050), elevated fasting glucose value (men and women, P < 0.001), and low HDL cholesterol level (men, P < 0.050; women, P < 0.010); a prevalence decrease was seen for high blood pressure (men and women, P < 0.001) and hypertriglyceridemia (men, P < 0.001; women, P < 0.010). CHD risk decreased marginally in men (P < 0.050) but did not change in women (P = 0.943).

CONCLUSIONS—Neither the prevalence of the metabolic syndrome nor CHD risk has increased in Mexico City. Lower blood pressure and triglyceride values appear to have counteracted increases in central obesity and fasting glucose.
High Plasma Level of Remnant-Like Particle Cholesterol in the Metabolic Syndrome
Authors: Satoh Akira , Adachi Hisashi , Tsuruta Makoto , Hirai Yuji , Hiratsuka Akiko , Enomoto Mika , Furuki Kumiko , Hino Asuka , Takeuchi Tomohiro , Imaizumi Tsutomu
Published: March 2007

OBJECTIVE—The metabolic syndrome is associated with a high incidence of cardiovascular disease even when the abnormalities present in the syndrome are mild. The underlying mechanism of the metabolic syndrome has not been elucidated. We investigated whether a strong atherogenic lipoprotein, remnant-like particle (RLP) lipoprotein cholesterol, is elevated in the metabolic syndrome.

RESEARCH DESIGN AND METHODS—We performed a health examination among the residents of a rural community in Japan. Complete datasets, including fasting RLP cholesterol levels, were obtained in 1,261 subjects (509 men and 752 women) without diabetes and who were not taking lipid-lowering drugs. The subjects’ medical history, use of alcohol, and smoking habits were ascertained by a questionnaire.

RESULTS—All of the components of the metabolic syndrome were significantly related to RLP cholesterol by univariate analysis. Total cholesterol and smoking habits were also positively associated with RLP cholesterol. The subjects with the metabolic syndrome showed only mild abnormalities of each component. When RLP cholesterol levels were stratified by the number of the components of the metabolic syndrome, there was a strong association between RLP cholesterol levels and the number of components (P < 0.001 and F = 72.7).

CONCLUSIONS—RLP cholesterol levels are elevated in the metabolic syndrome, and this elevation may underlie the high incidence of cardiovascular disease in the metabolic syndrome.
Restless Legs Syndrome and Quality of Sleep in Type 2 Diabetes
Authors: Lopes Lívia A. , Lins Camila de M.M. , Adeodato Vanessa G. , Quental Diana P. , de Bruin Pedro F.C. , Montenegro Renan M. , de Bruin Veralice M.S.
Published: March 2007

OBJECTIVE—To investigate the presence of restless legs syndrome (RLS) and the quality of sleep in a population of type 2 diabetic patients.

RESEARCH DESIGN AND METHODS—The study population was composed of 100 consecutive patients regularly attending a diabetes clinic at the University Hospital of the Federal University of Ceará. The subjects’ quality of sleep was assessed by the Pittsburgh Sleep Quality Index, and excessive daytime sleepiness (EDS) was measured by the Epworth Sleepiness Scale. The RLS was diagnosed using the four minimum criteria defined by the International Restless Legs Syndrome Study Group. Other relevant clinical and laboratory parameters were obtained by interview and chart review.

RESULTS—RLS was found in 27% of patients. Poor sleep quality was present in 45% of cases and was associated with age (P = 0.04), peripheral neuropathy (P = 0.001), and RLS (P = 0.000). EDS was found in 26% of patients. Logistic regression analysis revealed an association between RLS and peripheral neuropathy (odds ratio 12.85 [95% CI 2.83–58.40], P = 0.001).

CONCLUSIONS—RLS is common in type 2 diabetic patients and can be a major cause of sleep disruption in these patients.
The Effect of Ruboxistaurin on Nephropathy in Type 2 Diabetes
Authors: Tuttle Katherine R. , Bakris George L. , Toto Robert D. , McGill Janet B. , Hu Kuolung , Anderson Pamela W.
Published: March 2007

OBJECTIVE—Ruboxistaurin selectively inhibits protein kinase C-β and ameliorates kidney disease in animal models of diabetes. The purpose of this study was to evaluate the effects of ruboxistaurin on diabetic nephropathy in humans.

RESEARCH DESIGN AND METHODS—A randomized, double-blind, placebo-controlled, multicenter, pilot study was performed to evaluate the effects of 32 mg/day ruboxistaurin for 1 year in persons (n = 123) with type 2 diabetes and persistent albuminuria (albumin-to-creatinine ratio [ACR] 200-2,000 mg/g), despite therapy with renin-angiotensin system inhibitors. The primary end point was a change in the ACR. Estimated glomerular filtration rate (eGFR) (four-component equation from the Modification of Diet in Renal Disease study) was also calculated.

RESULTS—At baseline, urinary ACR was 764 ± 427 mg/g (means ± SD), and eGFR was 70 ± 24 ml/min per 1.73 m2. Systolic and diastolic blood pressures were 135 ± 14 and 75 ± 9 mmHg, respectively. HbA1c was 8.0 ± 1.2%. After 1 year, urinary ACR decreased significantly (−24 ± 9%) in participants treated with ruboxistaurin (P = 0.020) and nonsignificantly (−9 ± 11%) in the placebo group (P = 0.430). The ACR-lowering effect of ruboxistaurin appeared by 1 month. eGFR did not decline significantly in the ruboxistaurin group (−2.5 ± 1.9 ml/min per 1.73 m2) (P = 0.185), whereas the placebo group lost significant eGFR over 1 year (−4.8 ± 1.8 ml/min per 1.73 m2) (P = 0.009). Between-group differences for changes in ACR and eGFR were not statistically significant, but this pilot study was underpowered to determine such differences.

CONCLUSIONS—In persons with type 2 diabetes and nephropathy, treatment with ruboxistaurin reduced albuminuria and maintained eGFR over 1 year. Ruboxistaurin may add benefit to established therapies for diabetic nephropathy.
Laparoscopic Gastric Banding Prevents Type 2 Diabetes and Arterial Hypertension and Induces Their Remission in Morbid Obesity
Authors: Pontiroli Antonio E. , Folli Franco , Paganelli Michele , Micheletto Giancarlo , Pizzocri Pierluigi , Vedani Paola , Luisi Francesca , Perego Lucia , Morabito Alberto , Bressani Doldi Santo
Published: March 2007

OBJECTIVE—Lifestyle modifications and pharmacological interventions can prevent type 2 diabetes in obese subjects with impaired glucose tolerance. The aim of this study was to compare laparoscopic adjustable gastric banding (LAGB) and conventional diet (No-LAGB) in the prevention (primary intervention study; 56 vs. 29 patients) and remission (secondary intervention study; 17 vs. 20 patients) of type 2 diabetes and hypertension in grade 3 obesity in a 4-year study.

RESEARCH DESIGN AND METHODS—The subjects (n = 122; age 48.5 ± 1.05 years; BMI 45.7 ± 0.67 kg/m2) underwent a diagnostic workup, including psychological and psychiatric assessments, in preparation for the LAGB procedure. Of the 122 subjects, 73 had the surgery (LAGB group). The control group (No-LAGB group) consisted of the 49 subjects who refused the surgery but agreed to be followed up; 6 of these subjects dropped out by the 2nd year of the study, so that the final number of patients was 73 and 43 in the LAGB and No-LAGB groups, respectively. All patients had a yearly visit and oral glucose tolerance test.

RESULTS—From baseline to the end of the 4-year follow-up, BMI decreased from 45.9 ± 0.89 at baseline to 37.7 ± 0.71 kg/m2 in the LAGB group and remained steady in the No-LAGB group (from 45.2 ± 1.04 to 46.5 ± 1.37 kg/m2), with no significant differences between the primary and secondary intervention groups. In the primary intervention study, five of the No-LAGB subjects (17.2%) and none of the LAGB subjects (0.0%; P = 0.0001) progressed to type 2 diabetes; in the secondary intervention study, type 2 diabetes remitted in one No-LAGB patient (4.0%) and seven LAGB patients (45.0%; P = 0.0052). Hypertension occurred in 11 No-LAGB patients (25.6%) and 1 LAGB patient (1.4%; P = 0.0001) and remitted in 1 No-LAGB (2.3%) and 15 LAGB patients (20.5%; P = 0.0001). A study of body mass composition revealed a significant reduction of fat mass and a transitory, but not significant, decrease of fat-free mass in LAGB patients.

CONCLUSIONS—In morbid obesity, sustained and long-lasting weight loss obtained through LAGB prevents the occurrence of type 2 diabetes and hypertension and decreases the prevalence of these disorders.
Relative Risk of Mortality Associated With Diabetes as a Function of Birth Weight
Authors: Leibson Cynthia L. , Burke James P. , Ransom Jeanine E. , Forsgren Jessica , Melton Joseph , Bailey Kent R. , Palumbo Pasquale J.
Published: March 2007

OBJECTIVE—Birth weight is a risk factor for both diabetes and mortality. Diabetes is a risk factor for mortality. Whether the excess mortality observed for diabetes varies with birth weight is unclear.

RESEARCH DESIGN AND METHODS—Among all 2,508 Rochester, Minnesota, residents who first met research criteria for adult-onset diabetes in 1960–1995, 171 were born locally in-hospital after 1922 (i.e., birth weights available) as singleton, term infants. Each case subject and two age- and sex-matched nondiabetic control subjects (born locally, residing locally when the case subject met the criteria for diabetes) were followed through 31 December 2000 for vital status.

RESULTS—Of the diabetic case subjects, 16% (27 of 171) died vs. 7% (25 of 342) of control subjects (P = 0.004). The difference was less for normal-birth-weight (NBW) (2,948–<3,856 g) individuals (12% [12 of 102] vs. 8% [20 of 246], P = 0.31) than for abnormal-birth-weight individuals (low birth weight [LBW] 20% [8 of 39] vs. 2% [1 of 46], P = 0.01; high birth weight [HBW] 23% [7 of 30] vs. 8% [4 of 50], P = 0.16), as confirmed with age- and sex-adjusted Cox proportional hazards (diabetes-associated hazard ratio 1.4 [95% CI 0.69–2.90] for NBW vs. 4.8 [1.7–13.3] for abnormal birth weight, test for interaction P = 0.056). The observed diabetes deaths were greater than expected, based on mortality for the general population (27 vs. 13.3, P < 0.001), with 70% of excess deaths occurring among LBW (8 vs. 2.2, P < 0.001) and HBW (7 vs. 3.1, P = 0.03) individuals.

CONCLUSIONS—The excess mortality observed for diabetes appears disproportionately concentrated among abnormal-birth-weight individuals, thus identifying a subset of at-risk diabetic individuals and reinforcing the importance of NBW deliveries.
Rosiglitazone Improves Exercise Capacity in Individuals With Type 2 Diabetes
Authors: Regensteiner Judith G. , Bauer Timothy A. , Reusch Jane E.B.
Published: March 2007

OBJECTIVE—Although exercise is recommended as a cornerstone of treatment for type 2 diabetes, it is often poorly adopted by patients. We have noted that even in the absence of apparent cardiovascular disease, persons with type 2 diabetes have an impaired ability to carry out maximal exercise, and the impairment is correlated with insulin resistance and endothelial dysfunction. We hypothesized that administration of a thiazolidinedione (TZD) agent would improve exercise capacity in type 2 diabetes.

RESEARCH DESIGN AND METHODS—Twenty participants with uncomplicated type 2 diabetes were randomly assigned in a double-blind study to receive either 4 mg/day of rosiglitazone or matching placebo after baseline measurements to assess endothelial function (brachial artery diameter by brachial ultrasound), maximal oxygen consumption ([Vdot]o2max), oxygen uptake ([Vdot]o2) kinetics, and insulin sensitivity by hyperinsulinemic-euglycemic clamp. Measurements were reassessed after 4 months of treatment.

RESULTS—Participant groups did not differ at baseline in any measure. Rosiglitazone-treated participants (n = 10) had significantly improved [Vdot]o2max (19.8 ± 5.3 ml · kg−1 · min−1 before rosiglitazone vs. 21.2 ± 5.1 ml · kg−1 · min−1 after rosiglitazone, P < 0.01), insulin sensitivity, and endothelial function. A change in [Vdot]o2max correlated with improved insulin sensitivity measured by clamp (r = 0.68, P < 0.05) and with improved brachial artery diameter (r = 0.70, P < 0.05). Placebo-treated participants (n = 10) showed no changes in [Vdot]o2max (19.4 ± 5.2 ml · kg−1 · min−1 before rosiglitazone vs. 18.1 ± 5.3 ml · kg−1 · min−1 after rosiglitazone, NS) or brachial artery diameter.

CONCLUSIONS—This is the first known report showing that a TZD improved exercise function in type 2 diabetes. Whether this is due to the observed improvements in insulin sensitivity and/or endothelial function or to another action of the TZD class requires further exploration.
Hepatic Enzymes, the Metabolic Syndrome, and the Risk of Type 2 Diabetes in Older Men
Authors: Wannamethee Sasiwarang Goya , Shaper Andrew Gerald , Lennon Lucy , Whincup Peter H.
Published: March 2007

OBJECTIVE—We have examined the relationship between hepatic enzymes, the metabolic syndrome, insulin resistance, and type 2 diabetes and assessed the potential of hepatic enzyme measurements in determining diabetes risk.

RESEARCH DESIGN AND METHODS—We conducted a prospective study of 3,500 nondiabetic men aged 60–79 years who were followed-up for a mean period of 5 years and in whom there were 100 incident type 2 diabetes cases.

RESULTS—In cross-sectional analyses, alanine aminotransferase (ALT) and γ-glutamyltransferase (GGT) were strongly associated with obesity, insulin resistance, and the metabolic syndrome. Prospectively, the risk of type 2 diabetes significantly increased with increasing levels of ALT and GGT even after adjustment for confounders including BMI (top versus bottom quarter ALT: relative risk 2.72 [95% CI 1.47–5.02]; GGT: 3.68 [1.68–8.04]). Additional adjustment for insulin resistance attenuated the effects, but the relationships with ALT and GGT remained significant (1.91 [1.01–3.60] and 2.69 [1.21–5.97], respectively). Further adjustment for inflammatory markers (C-reactive protein) made minor differences. Among high-risk subjects (obese men or those with the metabolic syndrome), elevated GGT and ALT enhanced the prediction of diabetes risk.

CONCLUSIONS— Elevated levels of ALT and GGT within the normal range are independent predictors of type 2 diabetes in older men and are useful additional measures in identifying those at high risk of diabetes.
Comparison of Basal Insulin Added to Oral Agents Versus Twice-Daily Premixed Insulin as Initial Insulin Therapy for Type 2 Diabetes
Authors: Janka Hans U. , Plewe Gerd , Riddle Matthew C. , Kliebe-Frisch Christine , Schweitzer Matthias A. , Yki-Järvinen Hannele
Published: March 2007

OBJECTIVE—To compare the efficacy and safety of adding once-daily basal insulin versus switching to twice-daily premixed insulin in type 2 diabetic patients insufficiently controlled by oral antidiabetic agents (OADs).

RESEARCH DESIGN AND METHODS—In a 24-week, multinational, multicenter, open, parallel group clinical trial, 371 insulin-naïve patients with poor glycemic control (fasting blood glucose [FBG] ≥120 mg/dl, HbA1c 7.5–10.5%) on OADs (sulfonylurea plus metformin) were randomized to once-daily morning insulin glargine plus glimepiride and metformin (glargine plus OAD) or to 30% regular/70% human NPH insulin (70/30) twice daily without OADs. Insulin dosage was titrated to target FBG ≤100 mg/dl (both insulins) and predinner blood glucose ≤100 mg/dl (70/30 only) using a weekly forced-titration algorithm.

RESULTS—Mean HbA1c decrease from baseline was significantly more pronounced (−1.64 vs. −1.31%, P = 0.0003), and more patients reached HbA1c ≤7.0% without confirmed nocturnal hypoglycemia (45.5 vs. 28.6%, P = 0.0013) with glargine plus OAD than with 70/30. Similarly, FBG decrease was greater with glargine plus OAD (adjusted mean difference −17 mg/dl [–0.9 mmol/l], P < 0.0001), and more patients reached target FBG ≤100 mg/dl with glargine plus OAD than with 70/30 (31.6 vs. 15.0%, P = 0.0001). Glargine plus OAD patients had fewer confirmed hypoglycemic episodes than 70/30 patients (mean 4.07 vs. 9.87/patient-year, P < 0.0001).

CONCLUSIONS—Initiating insulin treatment by adding basal insulin glargine once daily to glimepiride plus metformin treatment was safer and more effective than beginning twice-daily injections of 70/30 and discontinuing OADs in type 2 diabetic patients inadequately controlled with OADs.
Long-Term Dual Blockade With Candesartan and Lisinopril in Hypertensive Patients With Diabetes
Authors: Andersen Niels H. , Poulsen Per. L , Knudsen Søren T. , Poulsen Steen H. , Eiskjær Hans , Hansen Klavs W. , Helleberg Kjeld , Mogensen Carl E.
Published: March 2007

OBJECTIVE—To assess and compare the long-term effects of the combination of candesartan and lisinopril with high-dose lisinopril on systolic blood pressure in patients with hypertension and diabetes.

RESEARCH DESIGN AND METHODS—This was a prospective, randomized, parallel-group, double-blind, double-dummy study with a 12-month follow-up. Drug therapy was either lisinopril 40 mg once daily or dual-blockade treatment with candesartan 16 mg once daily and lisinopril 20 mg once daily. The study comprised 75 type 1 and type 2 diabetic patients aged 35–74 years. The main outcome measures were seated and 24-h ambulatory systolic blood pressure.

RESULTS—Reduction in systolic blood pressure (24-h systolic blood pressure) reduction was obtained in both treatment arms (mean reduction at final follow-up: dual blockade 6 mmHg vs. lisinopril 2 mmHg), but no significant difference was found between dual-blockade and lisinopril 40 mg once daily (P = 0.10). Both treatments were generally well tolerated, and similar low rates of side effects were found in the two groups.

CONCLUSIONS—There was no statistically significant difference between lisinopril 40 mg once daily and lisinopril 20 mg in combination with candesartan 16 mg once daily in reducing systolic blood pressure in hypertensive patients with diabetes.
Pro-Active Call Center Treatment Support (PACCTS) to Improve Glucose Control in Type 2 Diabetes
Authors: Young Robert J. , Taylor Jean , Friede Tim , Hollis Sally , Mason James M. , Lee Pauline , Burns Edna , Long Andrew F. , Gambling Tina , New John P. , Gibson J. Martin
Published: March 2007

OBJECTIVE— To determine whether Pro-Active Call Center Treatment Support (PACCTS), using trained nonmedical telephonists supported by specially designed software and a diabetes nurse, can effectively improve glycemic control in type 2 diabetes.

RESEARCH DESIGN AND METHODS— A randomized controlled implementation trial of 1-year duration was conducted in Salford, U.K. The trial comprised 591 randomly selected individuals with type 2 diabetes. By random allocation, 197 individuals were assigned to the usual care (control) group and 394 to the PACCTS (intervention) group. Lifestyle advice and drug treatment in both groups followed local guidelines. PACCTS patients were telephoned according to a protocol with the frequency of calls proportional to the last HbA1c level. The primary outcome was absolute reduction in HbA1c, and the secondary outcome was the proportion of patients reducing HbA1c by at least 1%.

RESULTS— A total of 332 patients (84%) in the PACCTS group and 176 patients (89%) in the control group completed the study. Final HbA1c values were available in 374 patients (95%) in the PACCTS group and 180 patients (92%) in the usual care group. Compared with usual care, HbA1c improved by 0.31% (95% CI 0.11–0.52, P = 0.003) overall in the PACCTS patients. For patients with baseline HbA1c >7%, the improvement increased to 0.49% (0.21–0.77, P < 0.001), whereas in patients with baseline HbA1c <7% there was no change. The difference in the proportions of patients achieving a ≥1% reduction in HbA1c significantly favored the PACCTS intervention: 10% (4–16, P < 0.001) overall and 15% (7–24, P < 0.001) for patients with baseline HbA1c >7%.

CONCLUSIONS— In an urban Caucasian trial population with blood glucose HbA1c >7%, PACCTS facilitated significant improvement in glycemic control. Further research should extend the validity of findings to rural communities and other ethnic groups, as well as to smoking and lipid and blood pressure control.
Acceptability and Satisfaction With a Telecarer Approach to the Management of Type 2 Diabetes
Authors: Long Andrew F. , Gambling Tina , Young Robert J. , Taylor Jean , Mason James M. ,   on behalf of the PACCTS Team
Published: March 2007

OBJECTIVE—To examine patients’ views of the acceptability of and satisfaction with telephone care center support provided to improve blood glucose control in type 2 diabetes.

RESEARCH DESIGN AND METHODS—The Pro-Active Call-Center Treatment Support (PACCTS) Trial randomized patients from 47 general practices in a deprived urban area in northwest England to usual care or to proactive call center support in addition to usual care. Satisfaction with care was assessed in all 591 patients at baseline and the end of the study using the Diabetes Satisfaction and Treatment Questionnaire (DTSQ). Acceptability was assessed in 394 intervention patients after at least three proactive calls from the call center and at the end of the trial. A purposive sample of 25 patients took part in in-depth semistructured interviews.

RESULTS—The response rates to the questionnaires were 79% (DTSQ) and 65% (acceptability). Persons receiving the intervention continued to report high levels of satisfaction with their treatment (95% CI 32.3–33.2 at 1 year), and >90% strongly agreed or agreed that the telecarer approach was acceptable. Qualitative comments pointed to the importance of a personalized service; increased feelings of well-being, including confidence and self-control; help with problem-solving; and patients developing rapport and a strong bond with the telecarers.

CONCLUSIONS—A personalized PACCTS approach is acceptable to patients. A service giving priority to the interpersonal dimension leads to increased commitment from patients to improve long-term glycemic control.
Secondary Attack Rate of Type 1 Diabetes in Colorado Families
Authors: Steck Andrea K. , Barriga Katherine J. , Emery Lisa M. , Fiallo-Scharer Rosanna V. , Gottlieb Peter A. , Rewers Marian J.
Published: March 2007

OBJECTIVE—Families of children diagnosed with type 1 diabetes require counseling concerning type 1 diabetes risk in nondiabetic siblings and parents. No U.S. population–specific life-table risk estimates are currently available for parents, and those for siblings (2–6% by age 20 years) are based on family studies completed before 1987.

RESEARCH DESIGN AND METHODS—We analyzed family histories of 1,586 patients in Colorado with type 1 diabetes (83% non-Hispanic white, 10% Hispanic, and 7% other) diagnosed before 16 years of age and interviewed during 1999–2002. Families of probands with type 2, undetermined, or secondary diabetes (n = 53) or those with incomplete data (n = 137) were excluded. The median age at onset of the proband was 7.1 years and the median diabetes duration 3.5 years. Cumulative risk estimates were calculated using survival analysis for 2,081 full siblings and 3,016 biological parents.

RESULTS—In siblings, the overall risk of type 1 diabetes by age 20 years was 4.4%, but it was significantly (P < 0.0001) higher in siblings of probands diagnosed under age 7 years than in those diagnosed later. In parents, the overall risk by age 40 years was 2.6% and higher in fathers (3.6%) than in mothers (1.7%) of probands (P < 0.001). Similar to siblings, the risk was also higher (P = 0.006) in parents of probands diagnosed <7 years of age than in those diagnosed later.

CONCLUSIONS—Current risks of type 1 diabetes in Colorado siblings and parents of type 1 diabetic probands are higher than in the 1982 Pittsburgh study but similar to contemporary European rates. Recurrence risk of type 1 diabetes is significantly higher in first-degree relatives of probands diagnosed at a young age.
Residual β-Cell Function and Male/Female Ratio Are Higher in Incident Young Adults Than in Children
Authors: Bruno Graziella , Cerutti Franco , Merletti Franco , Cavallo-Perin Paolo , Gandolfo Enrico , Rivetti Marina , Runzo Cristina , Pinach Silvia , Pagano Gianfranco ,   The Piedmont Study Group for Diabetes Epidemiology
Published: March 2007

OBJECTIVE— The hypothesis of age-dependent variations in epidemiologic and clinical features at onset of type 1 diabetes has been assessed in the registry of the province of Turin, Italy.

RESEARCH DESIGN AND METHODS— The study base is the population 0–29 years of age of the province of Turin, in the period from 1984 to 2000. Islet cell antibody (ICA), GAD antibody (GADA), antibodies to protein tyrosine phosphatase (IA2), and C-peptide were measured in subgroups of the cohort.

RESULTS— One thousand fifty-six incident cases have been identified (completeness of ascertainment 98.1%). Rates per 100,000 person-years were similar in males and females in the age-group 0–14 years (10.7, 95% CI 9.5–12.0 vs. 9.8, 8.6–11.1). In the age-group 15–29 years, males had higher risk than females (7.7, 6.9–8.6 vs. 5.3, 4.6–6.1; rate ratio, 1.46, 95% CI 1.23–1.74; P = 0.00002). Fasting plasma C-peptide values (n = 575) were twofold lower in the age-group 0–14 years than in the age-group 15–29 years (0.10 vs. 0.23 nmol/l; P < 0.0001). Frequencies of ICA and IA2 positivities (n = 183) decreased with increasing age, whereas frequency of GADA positivity increased. Idiopathic cases were 12.6% and had higher mean values of fasting (0.28 vs. 0.14 nmol/l; P = 0.043) and stimulated C-peptide (0.59 vs. 0.34 nmol/l; P = 0.05). In logistic regression analyses, subjects with fasting C-peptide values in the upper quartile had higher likelihood of being older (odds ratio 1.20 for year, 95% CI 1.11–1.28), ICA negative (0.26, 0.10–0.70), and female (1.29, 0.48–3.42).

CONCLUSIONS— This study shows 1) sex differences in incidence rates in young adults; 2) better preserved β-cell function in young adults, in idiopathic cases (12%), and in ICA-negative cases; and 3) lower frequencies of ICA and IA2 positivities and higher frequency of GADA positivity in young adults than in children.
Quality of Diabetes Care in U.S. Academic Medical Centers
Authors: Grant Richard W. , Buse John B. , Meigs James B. ,   for the University HealthSystem Consortium (UHC) Diabetes Benchmarking Project Team
Published: March 2007

OBJECTIVE— To assess both standard and novel diabetes quality measures in a national sample of U.S. academic medical centers.

RESEARCH DESIGN AND METHODS— This retrospective cohort study was conducted from 10 January 2000 to 10 January 2002. It involved 30 U.S. academic medical centers, which contributed data from 44 clinics (27 primary care clinics and 17 diabetes/endocrinology clinics). For 1,765 eligible adult patients with type 1 or type 2 diabetes with at least two clinic visits in the 24 months before 10 January 2002, including one visit in the 6 months before 10 January 2002, we assessed measurement and control of HbA1c, blood pressure, and cholesterol and corresponding medical regimen changes at the most recent clinic visit.

RESULTS— In this ethnically and economically diverse cohort, annual testing rates were very high (97.4% for HbA1c, 96.6% for blood pressure, and 87.6% for total cholesterol). Fewer patients were at HbA1c goal (34.0% <7.0%) or blood pressure goal (33.0% <130/80 mmHg) than lipid goals (65.1% total cholesterol <200 mg/dl, 46.1% with LDL cholesterol <100 mg/dl). Only 10.0% of the cohort met recommended goals for all three risk factors. At the most recent clinic visit, 40.4% of patients with HbA1c concentrations above goal underwent adjustment of their corresponding regimens. Among untreated patients, few with elevated blood pressure (10.1% with blood pressure >130/80 mmHg) or elevated LDL cholesterol (5.6% with LDL >100 mg/dl) were started on corresponding therapy. Patients with type 2 diabetes were no less likely to be intensified than patients with type 1 diabetes.

CONCLUSIONS— High rates of risk factor testing do not necessarily translate to effective metabolic control. Low rates of medication adjustment among patients with levels above goal suggest a specific and novel target for quality improvement measurement.
Use of Methadone for the Treatment of Diabetic Neuropathy
Authors: Hays Lewis , Reid Coleen , Doran Michelle , Geary Karyn
Published: March 2007

Editor’s comment: This is the second Commentary of those that will appear from time to time describing treatments that may not have been validated by appropriate clinical trials but seem to be effective in diabetic patients based on small studies and/or extensive clinical experience. This one describes effective opioid treatment for those diabetic patients failing nonopioid therapies for painful neuropathy.
Comparison of Pioglitazone and Gliclazide in Sustaining Glycemic Control Over 2 Years in Patients With Type 2 Diabetes
Authors: Tan Meng H. , Baksi Arun , Krahulec Boris , Kubalski Piotr , Stankiewicz Andrzej , Urquhart Richard , Edwards Gareth , Johns Don ,   for the GLAL Study Group
Published: March 2007

OBJECTIVE—The hypothesis that pioglitazone treatment is superior to gliclazide treatment in sustaining glycemic control for up to 2 years in patients with type 2 diabetes was tested.

RESEARCH DESIGN AND METHODS—This was a randomized, multicenter, double-blind, double-dummy, parallel-group, 2-year study. Approximately 600 patients from 98 centers participated. Eligible patients had completed a previous 12-month study and consented to continue treatment for a further year. To avoid selection bias, all patients from all centers were included in the primary analysis (a comparison of the time-to-failure distributions of the two groups by using a log-rank test) regardless of whether they continued treatment for a 2nd year. By using repeated-measures ANOVA, time course of least square means of HbA1c and homeostasis model of assessment (HOMA) indexes (HOMA-%S and HOMA-%B) were analyzed.

RESULTS—A greater proportion of patients treated with pioglitazone maintained HbA1c <8% over the 2-year period than those treated with gliclazide. A difference between the Kaplan-Meier curves was apparent as early as week 32 and widened at each time point thereafter, becoming statistically significant from week 52 onward. At week 104, 129 (47.8%) of 270 pioglitazone-treated patients and 110 (37.0%) of 297 gliclazide-treated patients maintained HbA1c <8%. Compared with gliclazide treatment, pioglitazone treatment produced a larger decrease in HbA1c, a larger increase in HOMA-%S, and a smaller increase in HOMA-%B during the 2nd year of treatment.

CONCLUSIONS—Pioglitazone is superior to gliclazide in sustaining glycemic control in patients with type 2 diabetes during the 2nd year of treatment.
Effects of Exercise on the Absorption of Insulin Glargine in Patients With Type 1 Diabetes
Authors: Peter Rajesh , Luzio Stephen D. , Dunseath Gareth , Miles Andy , Hare Barry , Backx Karianne , Pauvaday Vassen , Owens David R.
Published: March 2007

OBJECTIVE—To study the effects of exercise on the absorption of the basal long-acting insulin analog insulin glargine (Lantus), administered subcutaneously in individuals with type 1 diabetes.

RESEARCH DESIGN AND METHODS—A total of 13 patients (12 men, 1 woman) with type 1 diabetes on a basal-bolus insulin regimen were studied. 125I-labeled insulin glargine at the usual basal insulin dose was injected subcutaneously into the thigh on the evening (2100) before the study day on two occasions 1 week apart. Patients were randomly assigned to 30 min intense exercise (65% peak oxygen uptake [Vo2peak]) on one of these visits. The decay of radioactive insulin glargine was compared on the two occasions using a thallium-activated Nal gamma counter. Blood samples were collected at regular intervals on the study days to assess plasma glucose and insulin profiles.

RESULTS—No significant difference was found in the 125I-labeled insulin glargine decay rate on the two occasions (exercise vs. no exercise; repeated-measures ANOVA, P = 0.548). As expected, a significant fall in plasma glucose was observed over the exercise period (area under curve above fasting [ΔAUC] glucose: −0.39 ± 0.11 vs. −1.30 ± 0.16 mmol · l−1 · h−1; nonexercise vs. exercise; P = 0.001), but insulin levels did not differ significantly on the two occasions (ΔAUC insulin: −2.1 ± 3.9 vs. 1.5 ± 6.2 pmol · l−1 · h−1; nonexercise versus exercise; P = 0.507).

CONCLUSIONS—An intense 30-min period of exercise does not increase the absorption rate of the subcutaneously injected basal long-acting insulin analog insulin glargine in patients with type 1 diabetes.
Diabetes and the Risk of Lung Cancer
Authors: Hall Gillian C. , Roberts C. Michael , Boulis Magdy , Mo Jingping , MacRae Kenneth D.
Published: March 2007

OBJECTIVE—The incidence of some cancers has been reported to be higher in diabetic patients than in the general population. We estimated the incidence of lung cancer in diabetic patients and investigated the hypothesis that the rate of lung cancer is different in diabetic compared with nondiabetic patients.

RESEARCH DESIGN AND METHODS—Diabetic patients and age-, sex-, and general practice-matched nondiabetic control subjects were identified from U.K. computerized general practice records (General Practice Research Database), and these records searched for any incident lung cancer, demographic details, and smoking status. Primary lung cancer incidence was calculated and rates compared between diabetic patients and nondiabetic control subjects using multivariate Cox regression, adjusting for age, sex, and smoking. The comparison was repeated for incident diabetic patients followed from diagnosis and after stratifying by diabetic treatment.

RESULTS—The incidence of primary lung cancer in all 66,848 diabetic patients was 1.63 per 1,000 patient-years (95% CI 1.48–1.79) and 2.05 per 1,000 patient-years (1.76–2.38) among diabetic patients followed from diagnosis. When compared with nondiabetic control subjects, the hazard ratio was 0.88 (0.79–0.97) for all diabetic patients and 1.12 (0.95–1.34) for those followed from diagnosis. When observation was truncated to allow for shorter life expectancy, the hazard ratio for the total cohort was 0.98 (0.84–1.13), and no association was found with any treatment group.

CONCLUSIONS—No increased risk of lung cancer in diabetes was found. We hypothesize that the lower incidence may be partly due to shorter life expectancy.
Clinical Inertia in Response to Inadequate Glycemic Control
Authors: Shah Baiju R. , Hux Janet E. , Laupacis Andreas , Zinman Bernard , van Walraven Carl
Published: March 2007

OBJECTIVE—Diabetic patients with inadequate glycemic control ought to have their management intensified. Failure to do so can be termed “clinical inertia.” Because data suggest that specialist care results in better control than primary care, we evaluated whether specialists demonstrated less clinical inertia than primary care physicians.

RESEARCH DESIGN AND METHODS—Using administrative data, we studied all non-insulin-requiring diabetic patients in eastern Ontario aged 65 or older who had A1c results >8% between September 1999 and August 2000. Drug intensification was measured by comparing glucose-lowering drug regimens in 4-month blocks before and after the elevated A1c test and was defined as 1) the addition of a new oral drug, 2) a dose increase of an existing oral drug, or 3) the initiation of insulin. Propensity score-based matching was used to control for confounding between groups.

RESULTS—There were 591 patients with specialist care and 1,911 with exclusively primary care. In the matched cohorts, 45.1% of patients with specialist care versus 37.4% with primary care had drug intensification (P = 0.009). Most of this difference was attributed to specialists’ more frequent initiation of insulin in response to elevated A1c.

CONCLUSIONS—Fewer than one-half of patients with high A1c levels had intensification of their medications, regardless of specialty of their physician. Specialists were more aggressive with insulin initiation than primary care physicians, which may contribute to the lower A1c levels seen with specialist care. Interventions assisting patients and physicians to recognize and overcome clinical inertia should improve diabetes care in the population.