bluuebunny/crossref_metadata_2025 huggingface dataset:
Estrogen Therapy and Risk of Cardiovascular Events Among Women With Type 2 Diabetes
Authors: Newton Katherine M. , LaCroix Andrea Z. , Heckbert Susan R. , Abraham Linn , McCulloch David , Barlow William
Published: March 2007

OBJECTIVE—To evaluate the association between estrogen therapy and cardiovascular disease risk among women with type 2 diabetes.

RESEARCH DESIGN AND METHODS—A retrospective, case-cohort study was conducted among 6,017 women aged 45–80 years with type 2 diabetes from 1 January 1986 to 31 December 1992 at the Group Health Cooperative in Washington state. Cardiovascular outcomes, including nonfatal myocardial infarction (n = 215), coronary revascularization (n = 253), and cardiovascular deaths (n = 229), were ascertained through 31 December 1998. Use of estrogen and progestin was derived from automated pharmacy records and modeled as a time-dependent variable. Median follow-up was 6.8 years. Multivariable-adjusted relative risk (RR) and 95% CI were calculated using Cox proportional hazard models for case-cohort analyses.

RESULTS—Current use of estrogen with (RR 0.43, 95% CI 0.22–0.85) or without (0.48, 0.30–0.78) progestin was associated with a decreased risk of cardiovascular events compared with never having used estrogen. Risk of cardiovascular events associated with a first episode of estrogen use (with or without progestin) of <25 months’ duration (1.12, 0.49–2.54), first episode of use ≥25 months’ duration (0.32, 0.06–1.70), and current use that was not the first episode of use (0.42, 0.42–0.67) indicated that recent initiation was not associated with an increase or decrease in risk.

CONCLUSIONS—These results show an association of estrogen therapy, with or without progestin, with decreased risk of cardiovascular events among women with type 2 diabetes. This association should be further investigated in large randomized, controlled trials.
Effects of 3 Months of Continuous Subcutaneous Administration of Glucagon-Like Peptide 1 in Elderly Patients With Type 2 Diabetes
Authors: Meneilly Graydon S. , Greig Nigel , Tildesley Hugh , Habener Joel F. , Egan Josephine M. , Elahi Dariush
Published: March 2007

OBJECTIVE—Glucagon-like peptide 1 (GLP-1) is an insulinotropic gut hormone that, when given exogenously, may be a useful agent in the treatment of type 2 diabetes. We conducted a 3-month trial to determine the efficacy and safety of GLP-1 in elderly diabetic patients.

RESEARCH DESIGN AND METHODS—A total of 16 patients with type 2 diabetes who were being treated with oral hypoglycemic agents were enrolled. Eight patients (aged 75 ± 2 years, BMI 27 ± 1 kg/m2) remained on usual glucose-lowering therapy and eight patients (aged 73 ± 1 years, BMI 27 ± 1 kg/m2), after discontinuing hypoglycemic medications, received GLP-1 delivered by continuous subcutaneous infusion for 12 weeks. The maximum dose was 120 pmol · kg−1 · h−1. Patients recorded their capillary blood glucose (CBG) levels (four times per day, 3 days per week) and whenever they perceived hypoglycemic symptoms. The primary end points were HbA1c and CBG determinations. Additionally, changes in β-cell sensitivity to glucose, peripheral tissue sensitivity to insulin, and changes in plasma ghrelin levels were examined.

RESULTS—HbA1c levels (7.1%) and body weight were equally maintained in both groups. The usual treatment group had a total of 87 CBG measurements of ≤3.6 mmol/l during the study, and only 1 such measurement (3.5 mmol/l) was recorded in the GLP-1 group. Infusion of GLP-1 enhanced glucose-induced insulin secretion (pre: 119 ± 21; post: 202 ± 51 pmol/l; P < 0.05) and insulin-mediated glucose disposal (pre: 29.8 ± 3.3; post: 35.9 ± 2.3 μmol · kg−1 · min−1; P < 0.01). No effect of GLP-1 treatment was seen on the fasting plasma ghrelin levels. Although plasma ghrelin levels decreased during both portions of the clamp, a drug effect was not present.

CONCLUSIONS—A GLP-1 compound is a promising therapeutic option for elderly diabetic patients.
Characterization of GLP-1 Effects on β-Cell Function After Meal Ingestion in Humans
Authors: Ahrén Bo , Holst Jens J. , Mari Andrea
Published: March 2007

OBJECTIVE—Glucagon-like peptide 1 (GLP-1) is an incretin that augments insulin secretion after meal intake and is developed for treatment of type 2 diabetes. As a novel therapeutic agent, characteristics of its β-cell effects are important to establish. Previously, β-cell effects of GLP-1 have been characterized in humans during graded intravenous infusions of glucose, whereas its effects after more physiological stimuli, like meal intake, are not known.

RESEARCH DESIGN AND METHODS—Eight women (aged 69 years, fasting glucose 3.7–10.3 mmol/l, BMI 22.4–43.9 kg/m2) who had fasted overnight were served a breakfast (450 kcal) with intravenous infusion of saline or synthetic GLP-1 (0.75 pmol · kg–1 · min–1), and β-cell function was evaluated by estimating the relationship between glucose concentration and insulin secretion (calculated by deconvolution of C-peptide data).

RESULTS—GLP-1 markedly augmented insulin secretion, despite lower glucose. Total insulin secretion was 29.7 ± 4.2 nmol/m2 with GLP-1 versus 21.0 ± 1.6 nmol/m2 with saline (P = 0.048). GLP-1 increased the dose-response relationship between glucose concentration and insulin secretion (70 ± 26 with GLP-1 versus 38 ± 16 pmol insulin · min−1 · m2 · mmol−1 glucose · l without, P = 0.037) and augmented the potentiation factor that modulates the dose response (2.71 ± 0.42 with GLP-1 versus 0.97 ± 0.17 without, P = 0.005). The potentiation factor correlated to GLP-1 concentration (r = 0.53, P < 0.001); a 10-fold increase in GLP-1 levels produced a twofold increase in the potentiation factor. These effects of GLP-1 did not correlate with fasting glucose levels or BMI.

CONCLUSIONS—Administration of GLP-1 along with ingestion of a meal augments insulin secretion in humans by a dose-dependent potentiation of the dose-response relationship between plasma glucose and insulin secretion.
Fasting Plasma Leptin, Tumor Necrosis Factor-α Receptor 2, and Monocyte Chemoattracting Protein 1 Concentration in a Population of Glucose-Tolerant and Glucose-Intolerant Women
Authors: Piemonti Lorenzo , Calori Giliola , Mercalli Alessia , Lattuada Guido , Monti Paolo , Garancini Maria Paola , Costantino Federica , Ruotolo Giacomo , Luzi Livio , Perseghin Gianluca
Published: March 2007

OBJECTIVE—Leptin and tumor necrosis factor (TNF)-α are associated with insulin resistance and cardiovascular disease. In vitro studies suggested that these effects may be mediated via overproduction of monocyte chemoattracting protein (MCP)-1/CCL2, which is a chemokine involved in the pathogenesis of atherosclerosis.

RESEARCH DESIGN AND METHODS—In this study, fasting plasma leptin, soluble TNF-α receptor 2 (TNF-α-R2), and MCP-1/CCL2 concentrations were measured in 207 middle-aged women (age 61 ± 12 years, BMI 30.1 ± 6.6 kg/m2), including 53 patients with type 2 diabetes, 42 with impaired glucose tolerance, and 112 with normal glucose tolerance, to assess cross-sectionally their relationship with markers of atherosclerosis and, longitudinally over 7 years, whether their circulating levels were associated with cardiovascular disease (CVD) mortality.

RESULTS—At baseline, leptin and TNF-α-R2 were not different among groups; meanwhile, MCP-1/CCL2 was increased in type 2 diabetes (P < 0.05). All showed significant associations with biochemical risk markers of atherosclerosis. In a univariate analysis, age, fasting insulin, leptin, and MCP-1/CCL2 were associated with CVD mortality at 7 years. When a multivariate analysis was performed, only age, leptin, and insulin retained an independent association with CVD mortality, with leptin showing a protective effect (hazard ratio 0.88; P < 0.02).

CONCLUSIONS—In middle-aged women, MCP-1/CCL2, leptin, and TNF-α-R2 were all related to biochemical risk markers of atherosclerosis. MCP-1/CCL2 concentration was the only one to be increased in type 2 diabetes with respect to nondiabetic women and the only one to be associated with increased risk of CVD mortality after a 7-year follow-up period in the univariate analysis. In the multivariate analysis, neither MCP-1/CCL2 nor TNF-α-R2 was associated with CVD mortality, and inspection of the data showed that leptin, in both the univariate and multivariate analysis, was associated with a protective effect.
Cardiorespiratory Fitness and the Incidence of Type 2 Diabetes
Authors: Sawada Susumu S. , Lee I-Min , Muto Takashi , Matuszaki Kazuko , Blair Steven N.
Published: March 2007

OBJECTIVE—To investigate the association between cardiorespiratory fitness and the incidence of type 2 diabetes among Japanese men.

RESEARCH DESIGN AND METHODS—This prospective cohort study was conducted in 4,747 nondiabetic Japanese men, aged 20–40 years at baseline, enrolled in 1985 with follow-up to June 1999. Cardiorespiratory fitness was measured using a cycle ergometer test, and Vo2max was estimated. During a 14-year follow-up, 280 men developed type 2 diabetes.

RESULTS—The age-adjusted relative risks of developing type 2 diabetes across quartiles of cardiorespiratory fitness (lowest to highest) were 1.0 (referent), 0.56 (95% CI 0.42–0.75), 0.35 (0.25–0.50), and 0.25 (0.17–0.37) (for trend, P < 0.001). After further adjustment for BMI, systolic blood pressure, family history of diabetes, smoking status, and alcohol intake, the association between type 2 diabetes risk and cardiorespiratory fitness was attenuated but remained significant (1.0, 0.78, 0.63, and 0.56, respectively; for trend, P = 0.001).

CONCLUSIONS—These results indicate that a low cardiorespiratory fitness level is an important risk factor for incidence of type 2 diabetes among Japanese men.
Pathways of Infant and Childhood Growth That Lead to Type 2 Diabetes
Authors: Eriksson Johan G. , Forsen Tom J. , Osmond Clive , Barker David J.P.
Published: March 2007

OBJECTIVE—Although a link between small body size at birth and later type 2 diabetes has been repeatedly documented, less is known about the associations between the disease and growth during infancy. The aim of this study was to explore the pathways of infant and early growth that lead to type 2 diabetes in adult life.

RESEARCH DESIGN AND METHODS—We carried out a longitudinal study of 8,760 subjects born in Helsinki from 1934 to 1944. On average, they had 8 measurements of height and weight between birth and 1 year of age and another 10 measurements between 1 and 12 years of age. We identified people with type 2 diabetes using a national register.

RESULTS—Among babies whose birth weights were ≤3.5 kg, the rate of infant growth was unrelated to later type 2 diabetes. Among babies with birth weights >3.5 kg, slow growth in length between birth and 3 months of age predicted later disease. Rapid gain in BMI after age 2 years increased the risk of later disease in both groups of babies, but this effect was greatest among children who had slow growth in length between birth and 3 months of age. In children whose Z-scores for length decreased, an SD increase in BMI at age 12 years was associated with an odds ratio (OR) for type 2 diabetes of 1.77 (95% CI 1.50–2.09). The corresponding OR in subjects whose Z-scores for length increased was 1.42 (95% CI 1.20–1.69). Rapid gain in childhood BMI was associated with high maternal BMI and socioeconomic factors (fewer people in the home and lower social class).

CONCLUSIONS—Babies with above-average birth weights may develop type 2 diabetes later in life if poor living conditions lead to faltering growth in length in the first few months after birth. We speculate that growth faltering at this time is associated with lifelong impairment of insulin metabolism and inability to meet the challenge of rapid childhood increase in BMI.
HBsAg Carrier Status and the Association Between Gestational Diabetes With Increased Serum Ferritin Concentration in Chinese Women
Authors: Lao Terence T. , Tse Ka-Yu , Chan Louis Y. , Tam Kar-Fai , Ho Lai-Fong
Published: March 2007

OBJECTIVE—To determine whether the high prevalence of hepatitis B surface antigen (HBsAg) carriage in our population can explain the previous observation of an association between increased maternal serum ferritin concentration and gestational diabetes in Hong Kong Chinese women.

RESEARCH DESIGN AND METHODS—A retrospective study was performed on 767 nonanemic women with singleton pregnancy who had iron status assessed at 28–30 weeks. The result of the routine antenatal HBsAg screening was retrieved from patient records. The HBsAg-positive and -negative groups were compared for maternal characteristics, prevalence of gestational diabetes in the third trimester, prevalence of high serum ferritin and iron concentrations, and transferrin saturation, which is defined as a value in the highest quartile established by the measurements obtained from the HBsAg-negative group.

RESULTS—The incidences of oral glucose tolerance test and gestational diabetes were significantly increased in the HBsAg-positive group. The HBsAg-positive women with gestational diabetes had significantly increased prevalence of high serum ferritin compared with the HBsAg-negative women, irrespective of the latter’s gestational diabetes status. Multiple logistic regression analysis confirmed the independent association between HBsAg carrier status with gestational diabetes (relative risk 3.51, 95% CI 1.83–6.73) but excluded high ferritin as an independent factor.

CONCLUSIONS—Our results indicate that maternal HBsAg carriage could explain in part the association between increased serum ferritin concentration with gestational diabetes in Hong Kong Chinese women, and that HBsAg carrier status is an independent risk factor for gestational diabetes.
Influence of Autonomic Nervous System Dysfunction on the Development of Type 2 Diabetes
Authors: Carnethon Mercedes R. , Jacobs David R. , Sidney Stephen , Liu Kiang
Published: March 2007

OBJECTIVE—We investigated whether autonomic nervous system dysfunction, estimated by slow heart rate recovery (HRR) following cessation of an exercise treadmill test, was associated with increases in insulin and glucose over time and the development of type 2 diabetes.

RESEARCH DESIGN AND METHODS—Maximal exercise tests were performed by 3,295 healthy adults aged 18–30 years in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Repeat measurements of insulin and glucose collected at 7-, 10-, and 15-year examinations were compared by quartiles of HRR (maximum heart rate minus heart rate 2 min after cessation of the test). Incident diabetes was identified at any follow-up examination as glucose ≥7 mmol/l or the use of diabetes control medication.

RESULTS—Among participants who did not develop diabetes, fasting insulin concentrations increased from baseline to year 15. Following adjustment (for age, race, sex, smoking status, and BMI), participants with the slowest HRR (quartile 1) had higher fasting insulin at each examination than participants with faster HRR (e.g., year 15 examination: 88.1 vs. 81.3 pmol/l for quartile 1 vs. quartile 4, respectively, P = 0.05). Glucose did not differ by quartile of HRR at any examination. Among participants with poor fitness, the risk of developing diabetes (n = 98) was 3.4-fold greater (95% CI 1.5–8.0) when HRR was <42 vs. >42 bpm. This persisted following adjustment for baseline insulin.

CONCLUSIONS—Autonomic dysfunction, in combination with poor physical fitness, may be a mechanism associated with early glucose dysmetabolism and the development of diabetes.
Symptoms of Common Maternal Infections in Pregnancy and Risk of Islet Autoimmunity in Early Childhood
Authors: Stene Lars C. , Barriga Katherine , Norris Jill M. , Hoffman Michelle , Klingensmith Georgeanna , Erlich Henry A. , Eisenbarth George S. , Rewers Marian
Published: March 2007

OBJECTIVE—The aim of this study was to test whether symptoms of maternal infections during pregnancy and indicators of postnatal infections predict development of islet autoimmunity in children at genetically increased risk of type 1 diabetes.

RESEARCH DESIGN AND METHODS—A total of 871 children with type 1 diabetes-associated HLA genotypes born in Denver, Colorado, and 391 siblings or offspring of individuals with type 1 diabetes referred from clinics in the Denver metropolitan area were enrolled soon after birth and seen in the clinic at age ≤15 months. Information on indicators of infection was collected by structured interviews soon after birth and at ages 3–15 months. Clinic visits were scheduled at ages 9, 15, and 24 months, and yearly thereafter. The outcome was positivity for one or more islet autoantibodies (to GAD65, insulin, or IA-2/ICA512) at two or more consecutive visits. During a mean follow-up of 4.2 years, 52 children developed islet autoimmunity.

RESULTS—Children whose mother reported at least one symptom of infection during pregnancy (mostly respiratory or gastrointestinal) had a significantly lower risk of islet autoimmunity compared with other children (hazard ratio 0.48; 95% CI 0.27–0.83). After stratification, the association appeared among girls (0.21; 0.09–0.48) but not among boys (1.09; 0.47–2.51) with a P value for interaction of 0.005. Symptoms of neonatal infections, early daycare attendance, exposure to cats or dogs, and household crowding were not related to islet autoimmunity.

CONCLUSIONS—Symptoms of maternal infections in pregnancy predicted a significantly lower risk of islet autoimmunity in young girls, suggesting a protective effect of such infections.
Enhancing Sensation in Diabetic Neuropathic Foot With Mechanical Noise
Authors: Khaodhiar Lalita , Niemi James B. , Earnest Russell , Lima Christina , Harry Jason D. , Veves Aristidis
Published: March 2007

OBJECTIVE—Localized low-level mechanical or electrical noise can significantly enhance tactile sensitivity in healthy young subjects and older adults. This phenomenon is termed stochastic resonance (SR). In this study, we examined the effect of SR on vibratory and tactile sensation in patients with moderate to severe diabetic peripheral neuropathy.

RESEARCH DESIGN AND METHODS—A total of 20 subjects were included in the study. The vibration perception threshold (VPT) test and the Semmes-Weinstein filament (SWF) threshold at the plantar surface of the left foot and the big toe were determined under two mechanical noise stimulus conditions: null (no noise) condition and at 10% lower than each subject’s mechanical noise threshold of perception.

RESULTS—The baseline values (mean ± SD) were as follows: Neuropathy Symptom Score (NSS) 5.2 ± 2.5, Neuropathy Disability Score (NDS) 5.0 ± 2.1, VPT 24 ± 11 V, and SWF threshold 5.6 ± 0.8 at the plantar surface of the foot and 5.3 ± 0.9 at the big toe. The VPT improved significantly from 24 ± 11 under null condition to 19 ± 10 V with mechanical noise (P < 0.0001). Mechanical noise also significantly increased the number of detections of the SWF at the plantar surface of the foot (detection rate 66 ± 11 vs. 59 ± 15%, P < 0.02) but not at the big toe (63 ± 10 vs. 61 ± 16%, P = NS).

CONCLUSIONS—Mechanical noise stimulation improves vibration and tactile perception in diabetic patients with moderate to severe neuropathy. Additional studies are required to examine the effect of long-term noise stimulation on parameters of nerve function.
Kidney Function During and After Withdrawal of Long-Term Irbesartan Treatment in Patients With Type 2 Diabetes and Microalbuminuria
Authors: Andersen Steen , Bröchner-Mortensen Jens , Parving Hans-Henrik ,   Irbesartan in Patients With Type 2 Diabetes and Microalbuminuria Study Group
Published: March 2007

OBJECTIVE—Irbesartan is renoprotective in patients with type 2 diabetes and microalbuminuria. Whether the observed reduction in microalbuminuria is reversible (hemodynamic) or persistent (glomerular structural/biochemical normalization) after prolonged antihypertensive treatment is unknown. Therefore, the present substudy of the Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria Study (IRMA-2) investigated the reversibility of kidney function changes after withdrawal of 2 years’ antihypertensive treatment.

RESEARCH DESIGN AND METHODS—The substudy included 133 hypertensive type 2 diabetic patients with persistent microalbuminuria in IRMA-2, randomized to double-masked treatment with either placebo, irbesartan 150 mg, or irbesartan 300 mg o.d. for 2 years. Arterial blood pressure, overnight urinary albumin excretion rate, and glomerular filtration rate (GFR) were determined repeatedly.

RESULTS—Baseline characteristics were similar in the placebo, irbesartan 150-mg, and irbesartan 300-mg groups. At the end of the study, mean arterial blood pressure (MABP) was similarly lowered to 105 ± 2 (mean ± SE), 103 ± 2, and 102 ± 2 mmHg, respectively (P < 0.05 versus baseline), and urinary albumin excretion rate reduced by 8% (−16 to 27) (NS), 34% (95% CI 8–53), and 60% (46–70) (P < 0.05). Rates of decline in GFR were 1.3 ± 0.7, 1.2 ± 0.7, and 1.0 ± 0.8 ml · min−1 · 1.73 m−2 per month, respectively, during the initial 3 months of the study and 0.3 ± 0.1, 0.3 ± 0.1, and 0.4 ± 0.1 ml · min−1 · 1.73 m−2 per month in the remaining study period. One month after withdrawal of all antihypertensive medication, MABP remained unchanged in the placebo group, 105 ± 2 mmHg, but increased significantly in the irbesartan groups, to 109 ± 2 and 108 ± 2 mmHg, respectively. Compared with baseline, urinary albumin excretion rate was increased by 14% (−17 to 54) in the placebo group and by 11% (−26 to 65) in the irbesartan 150-mg group but was persistently reduced by 47% (24–73) in the irbesartan 300-mg group (P < 0.05). GFR levels increased to baseline values in the placebo group and approached initial levels in irbesartan groups.

CONCLUSIONS—Persistent reduction of microalbuminuria after withdrawal of all antihypertensive treatment suggests that high-dose irbesartan treatment confers long-term renoprotective effects.
Outcome of Pregnancy Among Immigrant Women With Diabetes
Authors: Vangen Siri , Stoltenberg Camilla , Holan Synne , Moe Narve , Magnus Per , Harris Jennifer R. , Stray-Pedersen Babill
Published: March 2007

OBJECTIVE—We studied outcome of pregnancy among immigrant women with diabetes. The women came from regions of the world with high incidence of impaired glucose tolerance and type 2 diabetes. Prevalences, secular trends, and sociodemographic risk factors of diabetes were also explored.

RESEARCH DESIGN AND METHODS—Data from the Medical Birth Registry of Norway on all births from 1988 to 1998 for mothers born in South Asia and North Africa (11,268) and Norway (601,785) were analyzed.

RESULTS—The prevalence of pregestational diabetes among the immigrants was 8.9/1,000 births, which was more than twice the rate among ethnic Norwegians (3.6/1,000). Time trends indicated increasing prevalences in both groups. Among the immigrants, diabetes was closely associated with maternal age. Maternal diabetes was associated with a significantly increased risk of pregnancy complications in both study groups. Increased risks were found for low birth weight, macrosomia, preterm birth, preeclampsia, and cesarean sections. Among ethnic Norwegians, maternal diabetes conferred a significantly increased risk of infant perinatal death (odds ratio 2.00, 95% CI 1,44–2.77). In the sample of immigrant women with predominantly type 2 diabetes, maternal diabetes was not significantly associated with perinatal death or congenital malformations in the offspring.

CONCLUSIONS—The high prevalence of diabetes among immigrants from South Asia and North Africa represents a challenge for health care providers. To prevent adverse pregnancy outcomes and later cardiovascular and renal morbidity among these groups, early diagnosis of diabetes, adequate metabolic control, and relevant preventive measures are warranted.
Urinary α1-Microglobulin as a Marker of Nephropathy in Type 2 Diabetic Asian Subjects in Singapore
Authors: Hong Ching-Ye , Hughes Kenneth , Chia Kee-Seng , Ng Vivian , Ling Sing-Lin
Published: March 2007

OBJECTIVE—This study examines urinary α1-microglobulin as a marker of early nephropathy in type 2 diabetic Chinese, Malays, and Asian Indians in Singapore.

RESEARCH DESIGN AND METHODS—A cross-sectional study was performed on 590 consecutive type 2 diabetic patients (296 males, 294 females) who were on routine follow-up at a primary care clinic. Information was obtained from interviews, case notes, and blood and urine samples. Because the distribution of urinary α1-microglobulin levels was highly skewed, these levels were log-transformed, and geometric means were calculated. There was correction for variability in urine flow by dividing by urine creatinine levels, given as mg/mmol urine creatinine, and adjustment for confounding variables.

RESULTS—Urinary α1-microglobulin was higher in men than in women and was directly related to age, but no ethnic differences were apparent. It was directly related to duration of diabetes, with adjusted geometric means of 1.19 and 1.43 mg/mmol urine creatinine for a duration of <10 and ≥10 years, respectively (P = 0.07). Urinary α1-microglobulin was highest in patients on insulin, followed by those on oral medication and then those on diet alone (adjusted geometric means: 1.47, 1.36, and 0.86 mg/mmol urine creatinine, respectively; P = 0.01). Levels were also higher in patients with poor glucose control, as measured by HbA1c, fasting plasma glucose, and 2-h postprandial plasma glucose (P < 0.01 for each). Urinary α1-microglobulin was directly related to albuminuria, with adjusted geometric means for normoalbuminuria, microalbuminuria, and macroalbuminuria of 1.06, 1.47, and 4.72 mg/mmol urine creatinine, respectively (P < 0.01). However, of patients with normoalbuminuria, 33.6% had raised urinary α1-microglobulin. Likewise, of patients with normal urinary α1-microglobulin, 27.6% had albuminuria.

CONCLUSIONS—Urinary α1-microglobulin was related to duration, severity, and control of diabetes. Urinary α1-microglobulin and albumin were directly related, but in some patients, one was present in the absence of the other. Hence, in addition to albuminuria (which measures glomerular dysfunction), urinary α1-microglobulin (which measures proximal tubular dysfunction) is useful for the early detection of nephropathy in diabetic subjects.
Low Birth Weight and High Birth Weight Infants Are Both at an Increased Risk to Have Type 2 Diabetes Among Schoolchildren in Taiwan
Authors: Wei Jung-Nan , Sung Fung-Chang , Li Chung-Yi , Chang Chia-Hsuin , Lin Ruey-Shiung , Lin Chau-Ching , Chiang Chuan-Chi , Chuang Lee-Ming
Published: March 2007

OBJECTIVE—To study the effect of birth weight on risk of type 2 diabetes in the schoolchildren in Taiwan.

RESEARCH DESIGN AND METHODS—From 1992 to 1997, all schoolchildren aged 6–18 years were screened for diabetes in Taiwan Province. This cohort consisted of 1,966 patients with diabetes and 1,780 randomly selected subjects with normal fasting glycemia (NFG). Questionnaire interviewing was designed to classify diabetes. The birth weight was obtained from the Taiwan’s Birth Registry. After merging the data, there were 978 subjects, including 429 with type 2 diabetes and 549 with of NFG enrolled in the present analyses.

RESULTS—The odds ratios (95% CI) for type 2 diabetes, after adjusting age, sex, BMI, family history of diabetes, and socioeconomic status, were 2.91 (1.25–6.76) for children with low birth weight (<2,500 g) and 1.78 (1.04–3.06) for those with high birth weight (≥4,000 g) when compared with the referent group (birth weight 3,000–3,499 g). The risk of diabetes was still 64% higher in the high birth weight group [odds ratio (OR) 1.64 (95% CI 0.91–2.96)], even after adjustment for gestational diabetes mellitus (GDM). Patients with type 2 diabetes who were born with high birth weight were more likely to have a higher BMI and diastolic blood pressure as well as a higher family history of diabetes compared with those with low birth weight.

CONCLUSIONS—A U-shaped relationship between birth weight and risk of type 2 diabetes was found in the schoolchildren aged 6–18 years in Taiwan. Schoolchildren with type 2 diabetes who were born with low birth weight had different metabolic phenotypes compared with those born with high birth weight.
The Incidence of Retinopathy 10 Years After Diagnosis in Young Adult People With Diabetes
Authors: Henricsson Marianne , Nyström Lennarth , Blohmé Göran , Östman Jan , Kullberg Carin , Svensson Maria , Schölin Anna , Arnqvist Hans J. , Björk Elisabeth , Bolinder Jan , Eriksson Jan W. , Sundkvist Göran
Published: March 2007

OBJECTIVE—To estimate the prevalence and severity of diabetic retinopathy (DR) 10 years after diagnosis in a nationwide population-based cohort study of young adult diabetic patients in Sweden.

RESEARCH DESIGN AND METHODS—The Diabetes Incidence Study in Sweden (DISS) aims to register all incident cases of diabetes aged 15–34 years in Sweden. In 1987–1988, 806 cases were reported, and 627 (78%) of them were followed up with regard to retinopathy 8–10 years later. The assessment was based on retinal photographs in most cases (86%).

RESULTS—Ten years after diagnosis, retinopathy was found in 247 patients (39%). The retinopathy was mild in 206 (33%), whereas 30 (4.8%) patients had moderate nonproliferative DR (NPDR) and 11 (1.8%) had proliferative DR (PDR). Patients with retinopathy had worse glycemic control during the years than patients without (HbA1c 8.1 ± 1.5% and 6.8 ± 1.2%, respectively; P < 0.001). In a Cox regression analysis, time to retinopathy was related to high HbA1c (P < 0.001) and high BMI (P = 0.001). Patients with type 2 diabetes had an increased prevalence of severe retinopathy (NPDR or PDR) compared with those with type 1 diabetes (14 of 93 [15%] versus no or mild 24 of 471 [5%], respectively; P < 0.001).

CONCLUSIONS—Despite modern diabetes management, 39% of young adult diabetic patients developed retinopathy within the first 10 years of the disease. Nevertheless, compared with the prevalence of retinopathy (63%), after a similar duration of diabetes before the Diabetes Control and Complications Trial, this prevalence was clearly lower. Current treatment aimed to achieve strict glycemic control has reduced the risk for developing retinopathy.
Hypertension Management in Patients With Diabetes
Authors: Berlowitz Dan R. , Ash Arlene S. , Hickey Elaine C. , Glickman Mark , Friedman Robert , Kader Boris
Published: March 2007

OBJECTIVE—Clinical trials have demonstrated the importance of tight blood pressure control among patients with diabetes. However, little is known regarding the management of hypertension in patients with coexisting diabetes. To examine this issue, we addressed 1) whether hypertensive patients with coexisting diabetes are achieving lower levels of blood pressure than patients without diabetes, 2) whether there are differences in the intensity of antihypertensive medication therapy provided to patients with and without diabetes, and 3) whether diabetes management affects decisions to increase antihypertensive medication therapy.

RESEARCH DESIGN AND METHODS—We abstracted medical records to collect detailed information on 2 years of care provided for 800 male veterans with hypertension. We compared patients with and without diabetes on intensity of therapy and blood pressure control. Intensity of therapy was described using a previously validated measure that captures the likelihood of an increase in antihypertensive medications. We also determined whether increases in antihypertensive medications were less likely at those visits in which the diabetes medications were being adjusted.

RESULTS—Of the 274 hypertensive patients with diabetes, 73% had a blood pressure ≥140/90 mmHg, compared with 66% in the 526 patients without diabetes (P = 0.04). Diabetic patients also received significantly (P = 0.05) less intensive antihypertensive medication therapy than patients without diabetes. Less intensive therapy in diabetic patients could not be explained by clinicians being distracted by the treatment for diabetes.

CONCLUSIONS—There is an urgent need to improve hypertension care and blood pressure control in patients with diabetes. Additional information is required to understand why clinicians are not more aggressive in managing blood pressure when patients also have diabetes.
Validation of a Counseling Strategy to Promote the Adoption and the Maintenance of Physical Activity by Type 2 Diabetic Subjects
Authors: Di Loreto Chiara , Fanelli Carmine , Lucidi Paola , Murdolo Giuseppe , De Cicco Arianna , Parlanti Natascia , Santeusanio Fausto , Brunetti Paolo , De Feo Pierpaolo
Published: March 2007

OBJECTIVE—There is enough evidence that physical activity is an effective therapeutic tool in the management of type 2 diabetes. The present study was designed to validate a counseling strategy that could be used by physicians in their daily outpatient practice to promote the adoption and maintenance of physical activity by type 2 diabetic subjects.

RESEARCH DESIGN AND METHODS—The long-term (2-year) efficacy of the behavioral approach (n = 182) was compared with usual care treatment (n = 158) in two matched, randomized groups of patients with type 2 diabetes who had been referred to our Outpatient Diabetes Center. The outcome of the intervention was consistent patient achievement of an energy expenditure of >10 metabolic equivalents (METs)-h/week through voluntary physical activity.

RESULTS—After 2 years, 69% of the patients in the intervention group (27.1 ± 2.0 METs × h/week) and 18% of the control group (4.1 ± 0.8 METs × h/week) achieved the target (P < 0.001) with significant (P < 0.001) improvements in BMI (intervention group 28.9 ± 0.2 versus control group 30.4 ± 0.3 kg/m2) and HbA1c (intervention group 7.0 ± 0.1 versus control group 7.6 ± 0.1%).

CONCLUSIONS—This randomized, controlled study shows that physicians can motivate most patients with type 2 diabetes to exercise long-term and emphasizes the value of individual behavioral approaches in daily practice.
Maggot Therapy for Treating Diabetic Foot Ulcers Unresponsive to Conventional Therapy
Authors: Sherman Ronald A.
Published: March 2007

OBJECTIVE—To assess the efficacy of maggot therapy for treating foot and leg ulcers in diabetic patients failing conventional therapy.

RESEARCH DESIGN AND METHODS—Retrospective comparison of changes in necrotic and total surface area of chronic wounds treated with either maggot therapy or standard (control) surgical or nonsurgical therapy.

RESULTS—In this cohort of 18 patients with 20 nonhealing ulcers, six wounds were treated with conventional therapy, six with maggot therapy, and eight with conventional therapy first, then maggot therapy. Repeated measures ANOVA indicated no significant change in necrotic tissue, except when factoring for treatment (F [1.7, 34] = 5.27, P = 0.013). During the first 14 days of conventional therapy, there was no significant debridement of necrotic tissue; during the same period with maggot therapy, necrotic tissue decreased by an average of 4.1 cm2 (P = 0.02). After 5 weeks of therapy, conventionally treated wounds were still covered with necrotic tissue over 33% of their surface, whereas after only 4 weeks of therapy maggot-treated wounds were completely debrided (P = 0.001). Maggot therapy was also associated with hastened growth of granulation tissue and greater wound healing rates.

CONCLUSIONS—Maggot therapy was more effective and efficient in debriding nonhealing foot and leg ulcers in male diabetic veterans than was continued conventional care.
Aging Per Se Does Not Influence Glucose Homeostasis
Authors: Imbeault Pascal , Prins Johannes B. , Stolic Manuela , Russell Anthony W. , O’Moore-Sullivan Trisha , Després Jean-Pierre , Bouchard Claude , Tremblay Angelo
Published: March 2007

OBJECTIVE—To assess the effect of age on glucose metabolism by examining 1) glucose metabolism in young and middle-aged subjects when total or regional adiposity is taken into account and 2) in vitro glucose transport in adipose tissue explants from young and middle-aged women paired for total and abdominal adiposity.

RESEARCH DESIGN AND METHODS—Study 1: body composition, subcutaneous abdominal and visceral adipose tissue areas, and fasting and oral glucose–stimulated glucose and insulin were measured in 84 young and 81 middle-aged men and in 110 young and 91 middle-aged women. Study 2: glucose uptake in subcutaneous abdominal and visceral adipose tissue explants were measured in eight young and eight middle-aged women.

RESULTS—Study 1: young and middle-aged men showed similar subcutaneous abdominal tissue area, whereas fat mass and visceral adipose tissue were greater in middle-aged than in young men (P < 0.01). Fat mass and subcutaneous and visceral adipose tissue areas were greater in middle-aged as compared with young women (P < 0.01). Fasting plasma glucose and the glucose response to an oral glucose tolerance test were significantly higher in middle-aged than in young men and women (P < 0.001). Statistical control for visceral adipose tissue area eliminated the difference seen in glucose response in men and women. Study 2: glucose transport in subcutaneous and omental adipose tissue did not differ between young and middle-aged women.

CONCLUSIONS—1) Visceral obesity, more than age per se, correlates with glucose intolerance in middle-aged subjects; 2) aging does not influence in vitro adipose tissue glucose uptake.
Quality of Care for Diabetic Patients in a Large Urban Public Hospital
Authors: Suwattee Pitiporn , Lynch J. Christopher , Pendergrass Merri L.
Published: March 2007

OBJECTIVE—We compared diabetes quality-of-care indicators for patients receiving medical treatment in three practice settings of the same hospital.

RESEARCH DESIGN AND METHODS—A cross-sectional medical record review for patients receiving care between 1 July 2000 and 30 June 2001 was conducted. Records were abstracted from three practice settings: the Diabetes Clinic (DIABETES), a general medicine clinic staffed by internal medicine residents (RESIDENT), and a general medicine clinic whose providers were medical school faculty physicians (FACULTY). Record review (n = 791) yielded data on diabetes indicators that were derived primarily from the Diabetes Quality Improvement Project.

RESULTS—There were significant differences between the DIABETES, RESIDENT, and FACULTY clinics for the percentages of patients with HbA1c testing (94 vs. 92 vs. 76%, P < 0.001), HbA1c >9.5% (31 vs. 36 vs. 43%, P < 0.05), nephropathy assessment (79 vs. 67 vs. 58%, P < 0.001), lipid assessment (86 vs. 79 vs. 76%, P < 0.050), LDL <130 mg/dl (54 vs. 44 vs. 43%, P < 0.05), blood pressure <140/90 mmHg (63 vs. 55 vs. 49%, P < 0.025), eye examinations (64 vs. 50 vs. 31%, P < 0.001), foot examinations (97 vs. 55 vs. 24%, P < 0.001), ACE inhibitor treatment (66 vs. 69 vs. 35%, P < 0.001), and aspirin treatment (71 vs. 59 vs. 15%, P < 0.001).

CONCLUSIONS—There is considerable variation in diabetes management in different primary care settings of the same hospital. Although management in all settings was suboptimal, the results attained by the patients in the Diabetes Clinic represent minimal achievable goals for all diabetic patients in this hospital.
A Controlled Trial of Web-Based Diabetes Disease Management
Authors: Meigs James B. , Cagliero Enrico , Dubey Anil , Murphy-Sheehy Patricia , Gildesgame Catharyn , Chueh Henry , Barry Michael J. , Singer Daniel E. , Nathan David M.
Published: March 2007

OBJECTIVE—To test effects of a web-based decision support tool, the diabetes Disease Management Application (DMA), developed to improve evidence-based management of type 2 diabetes.

RESEARCH DESIGN AND METHODS—We conducted a group randomized controlled trial of 12 intervention and 14 control staff providers and 307 intervention and 291 control patients with type 2 diabetes in a hospital-based internal medicine clinic. Providers were randomly assigned from May 1998 through April 1999 to have access to the DMA (intervention) or not to have access (control). The DMA displays interactive patient-specific clinical data, treatment advice, and links to other web-based care resources. We compared patients in the intervention and control groups for changes in processes and outcomes of care from the year preceding the study through the year of the study by intention-to-treat analysis.

RESULTS—The DMA was used for 42% of scheduled patient visits. The number of HbA1c tests obtained per year increased significantly in the intervention group (+0.3 tests/year) compared with the control group (−0.04 tests/year, P = 0.008), as did the number of LDL cholesterol tests (intervention, +0.2 tests/year; control, +0.01 tests/year; P = 0.02) and the proportions of patients undergoing at least one foot examination per year (intervention, +9.8%; control, −0.7%; P = 0.003). Levels of HbA1c decreased by 0.2 in the intervention group and increased by 0.1 in the control group (P = 0.09); proportions of patients with LDL cholesterol levels <130 mg/dl increased by 20.3% in the intervention group and 10.5% in the control group (P = 0.5).

CONCLUSIONS—Web-based patient-specific decision support has the potential to improve evidence-based parameters of diabetes care.
Development of Congestive Heart Failure in Type 2 Diabetic Patients With Microalbuminuria or Proteinuria
Authors: Vaur Laurent , Gueret Pascal , Lievre Michel , Chabaud Sylvie , Passa Philippe ,   For the DIABHYCAR Study Group
Published: March 2007

OBJECTIVE—The DIABHYCAR (type 2 DIABetes, Hypertension, CArdiovascular Events and Ramipril) study allowed investigators to analyze factors leading to the development of congestive heart failure (CHF) in type 2 diabetic patients with abnormal urinary albumin concentration.

RESEARCH DESIGN AND METHODS—Type 2 diabetic subjects of both sexes aged ≥50 years who had a urinary albumin concentration ≥20 mg/l were randomly allocated to 1.25 mg/day ramipril or placebo in addition to their usual treatment and treated for 3–6 years in a double-blind fashion. Major outcomes including hospitalization for CHF were recorded during the follow-up.

RESULTS—Of the 4,912 included patients, 187 developed CHF during the study. There was no significant difference in the incidence of CHF between the two treatment groups. Using a multivariate analysis, independent risk factors for the occurrence of CHF were age, history of cardiovascular disease, baseline urinary albumin concentration, baseline HbA1c, and smoking habits. A total of 68 of the 187 patients (36.4%) died during the 12 ± 11-month period after the first hospitalization for CHF, whereas the annual mortality rate of the population who did not develop CHF was 3.2%.

CONCLUSIONS—Presence of atherosclerotic disease, baseline urinary albumin concentration, and HbA1c level were indicators for further development of CHF. Occurrence of CHF is a major prognostic turn in a diabetic patient’s life.
Contributions of Fasting and Postprandial Plasma Glucose Increments to the Overall Diurnal Hyperglycemia of Type 2 Diabetic Patients
Authors: Monnier Louis , Lapinski Hélène , Colette Claude
Published: March 2007

OBJECTIVE—The exact contributions of postprandial and fasting glucose increments to overall hyperglycemia remain controversial. The discrepancies between the data published previously might be caused by the interference of several factors. To test the effect of overall glycemic control itself, we analyzed the diurnal glycemic profiles of type 2 diabetic patients investigated at different levels of HbA1c.

RESEARCH DESIGN AND METHODS—In 290 non–insulin- and non–acarbose-using patients with type 2 diabetes, plasma glucose (PG) concentrations were determined at fasting (8:00 a.m.) and during postprandial and postabsorptive periods (at 11:00 a.m., 2:00 p.m., and 5:00 p.m.). The areas under the curve above fasting PG concentrations (AUC1) and >6.1 mmol/l (AUC2) were calculated for further evaluation of the relative contributions of postprandial (AUC1/AUC2, %) and fasting [(AUC2 − AUC1)/AUC2, %] PG increments to the overall diurnal hyperglycemia. The data were compared over quintiles of HbA1c.

RESULTS—The relative contribution of postprandial glucose decreased progressively from the lowest (69.7%) to the highest quintile of HbA1c (30.5%, P < 0.001), whereas the relative contribution of fasting glucose increased gradually with increasing levels of HbA1c: 30.3% in the lowest vs. 69.5% in the highest quintile (P < 0.001).

CONCLUSIONS—The relative contribution of postprandial glucose excursions is predominant in fairly controlled patients, whereas the contribution of fasting hyperglycemia increases gradually with diabetes worsening. These results could therefore provide a unifying explanation for the discrepancies as observed in previous studies.
A Prospective Study of Sugar Intake and Risk of Type 2 Diabetes in Women
Authors: Janket Sok-Ja , Manson JoAnn E. , Sesso Howard , Buring Julie E. , Liu Simin
Published: March 2007

OBJECTIVE—To investigate prospectively whether intake of total or type of sugar is associated with the risk of developing type 2 diabetes. The contribution of sugar intake to the pathogenesis of type 2 diabetes has not been settled in the context of primary prevention because of limited prospective data.

RESEARCH DESIGN AND METHODS—The Women’s Health Study is a randomized controlled trial of aspirin and vitamin E in the prevention of cardiovascular disease and cancer. A validated semiquantitative food frequency questionnaire was completed by 39,345 women aged 45 years and older. The main outcome was the incidence of type 2 diabetes. The predictor was sugar intake, including sucrose, glucose, fructose, and lactose. Using Cox proportional hazard models, multivariate RRs of type 2 diabetes for increasing quintiles of sugar intake compared with the lowest quintile were estimated.

RESULTS—Compared with the lowest quintile of sugar intake, the RRs and 95% CIs for the highest quintiles were 0.84 (0.67–1.04) for sucrose, 0.96 (0.78–1.19) for fructose, 1.04 (0.85–1.28) for glucose, and 0.99 (0.80–1.22) for lactose, after adjustment for known risk factors for type 2 diabetes. Similar findings of no association were obtained in subgroup analyses stratified by BMI.

CONCLUSIONS—Intake of sugars does not appear to play a deleterious role in primary prevention of type 2 diabetes. These prospective data support the recent American Diabetes Association’s guideline that a moderate amount of sugar can be incorporated in a healthy diet.
Evaluation of a Nurse-Care Management System to Improve Outcomes in Patients With Complicated Diabetes
Authors: Taylor C. Barr , Miller Nancy Houston , Reilly Kelly R. , Greenwald George , Cunning Darby , Deeter Allison , Abascal Liana
Published: March 2007

OBJECTIVE—This study evaluated the efficacy of a nurse-care management system designed to improve outcomes in patients with complicated diabetes.

RESEARCH DESIGN AND METHODS—In this randomized controlled trial that took place at Kaiser Permanente Medical Center in Santa Clara, CA, 169 patients with longstanding diabetes, one or more major medical comorbid conditions, and HbAlc >10% received a special intervention (n = 84) or usual medical care (n = 85) for 1 year. Patients met with a nurse-care manager to establish individual outcome goals, attended group sessions once a week for up to 4 weeks, and received telephone calls to manage medications and self-care activities. HbAlc, LDL, HDL, and total cholesterol, triglycerides, fasting glucose, systolic and diastolic blood pressure, BMI, and psychosocial factors were measured at baseline and 1 year later. Annualized physician visits were determined for the year before and during the study.

RESULTS—At 1 year, the mean reductions in HbAlc, total cholesterol, and LDL cholesterol were significantly greater for the intervention group compared with the usual care group. Significantly more patients in the intervention group met the goals for HbA1c (<7.5%) than patients in usual care (42.6 vs. 24.6%, P < 0.03, χ2). There were no significant differences in any of the psychosocial variables or in physician visits.

CONCLUSIONS—A nurse-care management program can significantly improve some medical outcomes in patients with complicated diabetes without increasing physician visits.