bluuebunny/crossref_metadata_2025 huggingface dataset:
Interactions Between Variants in the β3-Adrenergic Receptor and Peroxisome Proliferator–Activated Receptor-γ2 Genes and Obesity
Authors: Hsueh Wen-Chi , Cole Shelley A. , Shuldiner Alan R. , Beamer Brock A. , Blangero John , Hixson James E. , MacCluer Jean W. , Mitchell Braxton D.
Published: March 2007

OBJECTIVE—Previous studies have reported modest associations between measures of obesity and the Trp64Arg variant of the β3-adrenergic receptor (ADRβ3) and the Pro12Ala variant of the peroxisome proliferator–activated receptor (PPAR)-γ2. We hypothesized that these single gene variants may mark mutations that act through convergent pathways to produce synergistic effects on obesity.

RESEARCH DESIGN AND METHODS—The sample included 453 subjects from 10 large Mexican-American families participating in the population-based San Antonio Family Heart Study. The effects of each gene variant singly and jointly were estimated as fixed effects using the measured genotype approach framework. Analyses were conditioned on the pedigree structures to account for the correlations among family members. Statistical significance was evaluated by the likelihood ratio test with adjustment for age, sex, and diabetes status.

RESULTS—The allele frequencies for the ADRβ3 Trp64Arg and PPARγ2 Pro12Ala variants were 18 and 12%, respectively. The ADRβ3 variant was not significantly associated with any of the obesity-related traits, but subjects with the PPARγ2 variant (n = 98) had significantly higher levels of fasting insulin (P = 0.03), leptin (P = 0.009), and waist circumference (P = 0.03) than those without. Subjects with both gene variants (n = 32) had significantly higher BMI, insulin, and leptin levels than those with only the PPARγ2 variant (n = 66) (P for interaction: 0.04, 0.02, and 0.01 for BMI, fasting insulin, and leptin, respectively).

CONCLUSIONS—Our results suggest that epistatic models with genes that have modest individual effects may be useful in understanding the genetic underpinnings of typical obesity in humans.
Cardiovascular Morbidity and Mortality Associated With the Metabolic Syndrome
Authors: Isomaa Bo , Almgren Peter , Tuomi Tiinamaija , Forsén Björn , Lahti Kaj , Nissén Michael , Taskinen Marja-Riitta , Groop Leif
Published: March 2007

OBJECTIVE—To estimate the prevalence of and the cardiovascular risk associated with the metabolic syndrome using the new definition proposed by the World Health Organization (WHO).

RESEARCH DESIGN AND METHODS—A total of 4,483 subjects aged 35–70 years participating in a large family study of type 2 diabetes in Finland and Sweden (the Botnia study) were included in the analysis of cardiovascular risk associated with the metabolic syndrome. In subjects who had type 2 diabetes (n = 1,697), impaired fasting glucose (IFG)/impaired glucose tolerance (IGT) (n = 798), or insulin-resistance with normal glucose tolerance (NGT) (n = 1,988), the metabolic syndrome was defined as presence of at least two of the following risk factors: obesity, hypertension, dyslipidemia, or microalbuminuria. Cardiovascular mortality was assessed in 3,606 subjects with a median follow-up of 6.9 years.

RESULTS—In women and men, respectively, the metabolic syndrome was seen in 10 and 15% of subjects with NGT, 42 and 64% of those with IFG/IGT, and 78 and 84% of those with type 2 diabetes. The risk for coronary heart disease and stroke was increased threefold in subjects with the syndrome (P < 0.001). Cardiovascular mortality was markedly increased in subjects with the metabolic syndrome (12.0 vs. 2.2%, P < 0.001). Of the individual components of the metabolic syndrome, microalbuminuria conferred the strongest risk of cardiovascular death (RR 2.80; P = 0.002).

CONCLUSIONS—The WHO definition of the metabolic syndrome identifies subjects with increased cardiovascular morbidity and mortality and offers a tool for comparison of results from different studies.
α-Dicarbonyls Increase in the Postprandial Period and Reflect the Degree of Hyperglycemia
Authors: Beisswenger Paul J. , Howell Scott K. , O’Dell Rita M. , Wood Mary E. , Touchette Allison D. , Szwergold Benjamin S.
Published: March 2007

OBJECTIVE—Chronic hyperglycemia is known to increase tissue glycation and diabetic complications, but controversy exists regarding the independent role of increased postprandial glucose excursions. To address this question, we have studied the effect of postprandial glycemic excursions (PPGEs) on levels of methylglyoxal (MG) and 3-deoxyglucosone (3-DG), two highly reactive precursors of advanced glycation end products (AGEs).

RESEARCH DESIGN AND METHODS—We performed 4-month crossover studies on 21 subjects with type 1 diabetes and compared the effect of premeal insulin lispro or regular insulin on PPGEs and MG/3-DG excursions. PPGE was determined after standard test meal (STMs) and by frequent postprandial glucose monitoring. HbA1c and postprandial MG and d-lactate were measured by HPLC, whereas 3-DG was determined by gas chromatography/mass spectroscopy.

RESULTS—Treatment with insulin lispro resulted in a highly significant reduction in PPGEs relative to the regular insulin–treated group (P = 0.0005). However, HbA1c levels were similar in the two groups, and no relationship was observed between HbA1c and PPGE (P = 0.93). Significant postprandial increases in MG, 3-DG, and d-lactate occurred after the STM. Excursions of MG and 3-DG were highly correlated with levels of PPGE (R = 0.55, P = 0.0002 and R = 0.61, P = 0.0004; respectively), whereas a significant inverse relationship was seen between PPGE and d-lactate excursions (R = 0.40, P = 0.01). Conversely, no correlation was observed between HbA1c and postprandial MG, 3-DG, or d-lactate levels.

CONCLUSIONS—Increased production of MG and 3-DG occur with greater PPGE, whereas HbA1c does not reflect these differences. Reduced PPGE also leads to increased production of d-lactate, indicating a role for increased detoxification in reducing MG levels. The higher postprandial levels of MG and 3-DG observed with greater PPGE may provide a partial explanation for the adverse effects of glycemic lability and support the value of agents that reduce glucose excursions.
Midpregnancy Serum C-Peptide Concentration and Subsequent Pregnancy-Induced Hypertension
Authors: Yasuhi Ichiro , Hogan Joseph W. , Canick Jacob , Sosa Maryellen B. , Carpenter Marshall W.
Published: March 2007

OBJECTIVE—To test the hypothesis that elevated midpregnancy serum insulin (IRI) and C-peptide (CP) concentrations are associated with later development of pregnancy-induced hypertension (PIH), independent of prepregnancy obesity and midpregnancy blood pressure.

RESEARCH DESIGN AND METHODS—In this prospective study, a cohort of normotensive women, ages ≥18 years, performed a 50-g glucose challenge test at 24–30 weeks’ gestational age. Blood samples were collected after an overnight fast and 1 h after glucose ingestion. Serum IRI and CP concentrations were measured in each sample. Maternal height, blood pressure, and proteinuria were measured at the time of glucose challenge testing and after 36 weeks’ gestational age.

RESULTS—Of 320 subjects enrolled, 44 women (13.8%) had subsequent PIH. Crude odds ratios (ORs) for development of PIH associated with each 1 U rise in log fasting IRI, log fasting CP, and glucose-induced increase in CP (expressed as log [postprandial CP/fasting CP]) were 2.0 (95% CI 1.3–3.3), 1.8 (CI 1.2–2.7), and 2.3 (CI 1.1–4.9), respectively. After controlling for prepregnancy BMI, gestational age, and midpregnancy mean arterial pressure, adjusted ORs corresponding to log fasting IRI and CP for the development of PIH were 1.3 (95% CI 0.7–2.3) and 1.7 (CI 1.1–2.7), respectively, and, after adjustment for fasting CP, the adjusted OR of the glucose-induced rise in log CP was 3.7 (CI 1.5–9.3).

CONCLUSIONS—Mid-pregnancy fasting and postoral glucose CP levels are associated with subsequent development of PIH, independent of maternal obesity and midpregnancy baseline blood pressure. These findings may reflect an amplified β-cell response to glycemic stimulus, similar to that found in states of insulin resistance, that appears to be independently associated with PIH.
Glucose Metabolism in Pregnancy at High Altitude
Authors: Krampl Elisabeth , Kametas Nikolaos A. , Nowotny Peter , Roden Michael , Nicolaides Kypros H.
Published: March 2007

OBJECTIVE—To assess insulin sensitivity and β-cell function associated with lower maternal fasting plasma glucose levels at high altitude compared with sea level.

RESEARCH DESIGN AND METHODS—We studied 215 pregnant women at 8–42 weeks of gestation in Peru. The women were recruited from Cerro de Pasco, which is situated 4,370 m (14,340 feet) above sea level, and Lima, which is at sea level. We also examined 53 nonpregnant control subjects (22 in Cerro de Pasco and 31 in Lima). Fasting plasma glucose, insulin, C-peptide, and proinsulin concentrations were measured in samples obtained from the antecubital vein between 8:00 a.m. and 10:00 a.m. after an overnight period of fasting for 10–14 h. Insulin resistance and β-cell function were calculated using homeostasis model assessment.

RESULTS—Fasting C-peptide levels and β-cell function were similar, fasting concentrations of insulin and proinsulin were lower, and insulin sensitivity was higher at high altitude compared with sea level.

CONCLUSIONS—Maternal fasting plasma glucose that is lower at high altitude than at sea level in the presence of similar insulin secretion is associated with higher peripheral insulin sensitivity. This may partly explain the lower birth weights at high altitudes.
Hyperinsulinemia Predicts Fatal Liver Cancer but Is Inversely Associated With Fatal Cancer at Some Other Sites
Authors: Balkau Beverley , Kahn Henry S. , Courbon Dominique , Eschwège Eveline , Ducimetière Pierre
Published: March 2007

OBJECTIVE—To investigate whether insulin is a risk factor for death by site-specific cancers.

RESEARCH DESIGN AND METHODS—This was a prospective cohort study of 6,237 nondiabetic French working men between ages 44 and 55 years at baseline from the Paris Prospective Study cohort. Death by site-specific cancers was investigated in relation to baseline insulin concentrations during fasting and 2 h after a 75-g oral glucose tolerance test.

RESULTS—Of the original 6,237 men in the cohort, 1,739 died over the 23.8 years of follow-up, 778 (45%) from cancer. Baseline hyperinsulinemia, both fasting and 2-h, was significantly associated with fatal liver cancer, with age-adjusted standardized hazards ratios of 2.72 (95% CI 1.87–3.94) and 3.41 (2.23–5.21). In contrast, fasting hyperinsulinemia was inversely associated with fatal lip, oral cavity, and pharynx cancer and larynx cancer, with hazards ratios of 0.55 (0.41–0.75) and 0.63 (0.47–0.83), respectively; 2-h insulin concentrations were inversely associated with stomach and larynx cancers (hazards ratios 0.62 [0.43–0.90] and 0.66 [0.50–0.89], respectively). These relationships were stable after adjusting for other risk factors. Insulin concentrations remained negatively associated with deaths from these cancers in analyses restricted to men who smoked and in those who were not chronic alcohol consumers.

CONCLUSIONS—Peripheral hyperinsulinemia, indicative of very high portal insulin concentrations, predicted fatal liver cancer in these nondiabetic men, but was inversely associated with fatal lip, oral cavity, and pharynx cancer; stomach cancer; and larynx cancer.
Detection of Hypoglycemia With the GlucoWatch Biographer
Authors: Pitzer Kenneth R. , Desai Shashi , Dunn Tim , Edelman Steve , Jayalakshmi Yalia , Kennedy John , Tamada Janet A. , Potts Russell O.
Published: March 2007

OBJECTIVE—Hypoglycemia is a common acute complication of diabetes therapy. The GlucoWatch biographer provides frequent and automatic glucose measurements with an adjustable low-glucose alarm. We have analyzed the performance of the biographer low-glucose alarm relative to hypoglycemia as defined by blood glucose ≤3.9 mmol/l.

RESEARCH DESIGN AND METHODS—The analysis was based on 1,091 biographer uses from four clinical trials, which generated 14,487 paired (biographer and blood glucose) readings.

RESULTS—The results show that as the low-glucose alert level of the biographer is increased, the number of true positive alerts (alarm sounds and blood glucose ≤3.9 mmol/l) and false positive alerts (alarm sounds but blood glucose >3.9 mmol/l) increased. When analyzed as a function of varying low-glucose alert levels, the results show receiver operator characteristic curves consistent with a highly useful diagnostic tool. Setting the alert level from 1.1 to 1.7 mmol/l above the level of concern is likely to optimize the trade-off between true positives and false positives for each user. When the same blood glucose data are analyzed for typical monitoring practices (two or four measurements per day), the results show that fewer hypoglycemic events are detected than those detected with the biographer.

CONCLUSIONS—The frequent and automatic nature of the biographer readings allows more effective detection of hypoglycemia than that achieved with current medical practice.
Increased Collagen IV Excretion in Diabetes
Authors: Cohen Margo P. , Lautenslager Gregory T. , Shearman Clyde W.
Published: March 2007

OBJECTIVE—Increased albumin excretion in diabetes is believed to be derived from hemodynamic and/or permeability abnormalities, whereas mesangial matrix expansion gives rise to the reduction in glomerular filtration surface and decline in renal function in diabetic nephropathy. We postulated that the overproduction of extracellular matrix proteins underlying glomerulosclerosis in diabetes might be associated with the excretion of increased amounts of type IV collagen in the urine.

RESEARCH DESIGN AND METHODS—To explore this hypothesis, we measured the urinary excretion of (human) collagen IV by immunoassay in 65 patients with type 1 or type 2 diabetes and various degrees of albuminuria and examined its relationship to filtration function assessed by the reciprocal of the serum creatinine (RSC).

RESULTS—Collagen IV excretion showed a significant (P < 0.001) inverse correlation (r = −0.62) with the RSC, and this correlation pertained regardless of whether albumin excretion was in the low (≤100 μg/mg creatinine; r = −0.73) or high (>100 μg/mg; r = −0.53) range. In contrast, albumin excretion showed insignificant correlation with either collagen IV excretion (r = 0.12) or with the RSC (r = −0.20). Urinary collagen IV was significantly higher (P < 0.05) in patients with an RSC value ≤100 (28.3 ± 2.4 ng/mg creatinine) than in patients with an RSC value >100 (16.0 ± 0.8 ng/mg creatinine).

CONCLUSIONS—Because not all patients with microalbuminuria progress to declining renal function and some patients who develop nephropathy do not manifest albuminuria, the findings in this cross-sectional analysis suggest that measurement of urine collagen IV may be a useful noninvasive indicator to detect diabetic renal disease entering a phase of compromised renal function.
Type 2 Diabetes and Cognitive Function in Community-Dwelling Elderly Women
Authors: Grodstein Francine , Chen Jennifer , Wilson Robert S. , Manson JoAnn E.
Published: March 2007

OBJECTIVE—To examine the relationship of type 2 diabetes to cognitive function in community-dwelling women.

RESEARCH DESIGN AND METHODS—From 1995 to 1999, we administered four tests of cognitive function (Telephone Interview of Cognitive Status [TICS], immediate and delayed recall of the East Boston Memory Test, and verbal fluency) by telephone to 2,374 participants (70–78 years of age) of the Nurses’ Health Study. Information on diabetes was collected biennially beginning in 1976; 82 women reported type 2 diabetes before their cognitive testing. We used linear and logistic regression models to calculate multivariate-adjusted mean differences in scores and relative risks of a low score (bottom 10% of the distribution) for diabetic women compared with nondiabetic women.

RESULTS—After multivariate adjustment, women with type 2 diabetes scored lower on all our cognitive tests than women without diabetes. On the general test of cognition (TICS), the mean difference in score between women with and without diabetes was −0.60 (95% CI −1.18 to –0.03, P = 0.04) and the relative risk of a low TICS score was 1.98 (95% CI 1.06 to 3.69). On a global score combining results of the four tests, the mean for diabetic women was lower than that among women without diabetes (adjusted difference in score −0.73, 95% CI −1.42 to −0.04, P = 0.04), and the relative risk of a low global score was 2.16 (95% CI 1.10 to 4.21). Relative to women without diabetes, longer duration of diabetes was associated with lower scores. Few diabetic women were pharmacologically treated (n = 31), but those taking medication had scores similar to those of women without diabetes.

CONCLUSIONS—In these women, diabetes was related to lower scores on several aspects of cognitive function. Longer duration of diabetes may be associated with poorer scores, but hypoglycemic therapy may ameliorate scores.
Peripheral Nerve Function Is Increasingly Impaired During Puberty in Adolescents With Type 1 Diabetes
Authors: Riihimaa Päivi H. , Suominen Kalervo , Tolonen Uolevi , Jäntti Ville , Knip Mikael , Tapanainen Päivi
Published: March 2007

OBJECTIVE—To evaluate the impact of puberty on peripheral nerve function in adolescents with type 1 diabetes.

RESEARCH DESIGN AND METHODS—Of 138 eligible patients with type 1 diabetes, 100 patients (age >9 years and diabetes duration >2 years) attending an outpatient diabetes clinic and 100 age- and sex-matched healthy control subjects took part in this cross-sectional study. Peripheral motor and sensory nerve conduction tests, cardiovascular reflex tests on the autonomic nervous system, and measurements of vibration-perception threshold (VPT) were performed.

RESULTS—Nerve conduction velocity (NCV) in the distal motor and sensory nerves, the motor nerve distal latency, and the sensory nerve action potential (SNAP) amplitude were impaired in the adolescent patients with type 1 diabetes. The deterioration in motor NCV, H-reflex latency, and SNAP amplitude became more conspicuous in late puberty and postpuberty and was related to poor metabolic control. A total of 10 patients had distal diabetic polyneuropathy (DP) neurophysiologically, and these patients had significantly lower heart-rate variation in the deep breathing test than the other patients. Three of the patients with DP had peripheral neurological signs or symptoms. A slight difference in the VPT between the patients and control subjects was observed after puberty.

CONCLUSIONS—Increasing subclinical motor nerve impairment can be detected during late puberty and after puberty, and sensory NCV and SNAP amplitude are reduced in adolescents with type 1 diabetes. Poor metabolic control during puberty appears to induce deteriorating peripheral neural function in young patients with type 1 diabetes.
Aldose Reductase Inhibition Ameliorates Pupillary Light Reflex and F-Wave Latency in Patients With Mild Diabetic Neuropathy
Authors: Nakayama Mikihiro , Nakamura Jiro , Hamada Yoji , Chaya Sadao , Mizubayashi Ryuichi , Yasuda Yutaka , Kamiya Hideki , Koh Naoki , Hotta Nigishi
Published: March 2007

OBJECTIVE—The present study was conducted to investigate the effect of an aldose reductase inhibitor, epalrestat, on autonomic and somatic neuropathy at an early stage in type 2 diabetic patients by assessing the pupillary light reflex and minimum latency of the F-wave.

RESEARCH DESIGN AND METHODS—A total of 30 diabetic patients with subclinical or mild diabetic neuropathy were randomly allocated to a control group (n = 15) and epalrestat (150 mg/day) group (n = 15). After 24 weeks, the pupillary light reflex test, cardiovascular autonomic function tests, and nerve conduction study were performed.

RESULTS—The beneficial effect of epalrestat on the pupillary light reflex was observed in the minimum diameter after light stimuli (P = 0.044), constriction ratio (P = 0.014), and maximum velocity of constriction (P = 0.008). Among cardiovascular autonomic nerve functions, the ratio of the longest expiratory R-R interval to the shortest inspiratory R-R interval during deep breathing was significantly improved by epalrestat (P = 0.037). Minimum latencies of F-wave of median and tibial motor nerves were significantly shortened by epalrestat (P = 0.002 and P = 0.001, respectively); however, no significant effects were observed in motor or sensory nerve conduction velocity.

CONCLUSIONS—These observations suggest that epalrestat may have therapeutic value at the early stage of diabetic neuropathy and that the pupillary light reflex and minimum latency of F-wave may be useful indicators of diabetic neuropathy.
Frequency of Blood Glucose Monitoring in Relation to Glycemic Control in Patients With Type 2 Diabetes
Authors: Harris Maureen I.
Published: March 2007

OBJECTIVE—The aim of the study was to investigate the relationship between blood glucose level, measured as HbA1c, and frequency of self-monitoring in patients with type 2 diabetes. Daily self-monitoring is believed to be important for patients treated with insulin or oral agents to detect asymptomatic hypoglycemia and to guide patient and provider behavior toward reaching blood glucose goals.

RESEARCH DESIGN AND METHODS—A national sample of patients with type 2 diabetes was studied in the third National Health and Nutrition Examination Survey. Data on therapy for diabetes, frequency of self-monitoring of blood glucose, and HbA1c values were obtained by structured questionnaires and by clinical and laboratory assessments.

RESULTS—According to the data, 29% of patients treated with insulin, 65% treated with oral agents, and 80% treated with diet alone had never monitored their blood glucose or monitored it less than once per month. Self-monitoring at least once per day was practiced by 39% of those taking insulin and 5–6% of those treated with oral agents or diet alone. For all patients combined, the proportion of patients who tested their blood glucose increased with an increasing HbA1c value. However, when examined by diabetes therapy category, there was little relationship between HbA1c value and the proportion testing at least once per day or the proportion testing at least once per week.

CONCLUSIONS—In this cross-sectional study of patients with type 2 diabetes, the increase in frequency of self-monitoring of blood glucose with increasing HbA1c value was associated with the higher proportion of insulin-treated patients in higher HbA1c categories. Within diabetes therapy categories, the frequency of self-monitoring was not related to glycemic control, as measured by HbA1c level.
Hormone Replacement Therapy Is Associated With Better Glycemic Control in Women With Type 2 Diabetes
Authors: Ferrara Assiamira , Karter Andrew J. , Ackerson Lynn M. , Liu Jennifer Y. , Selby Joseph V.
Published: March 2007

OBJECTIVE—In women with diabetes, the changes that accompany menopause may further diminish glycemic control. Little is known about how hormone replacement therapy (HRT) affects glucose metabolism in diabetes. The aim of this study was to examine whether HbA1c levels varied by current HRT among women with type 2 diabetes.

RESEARCH DESIGN AND METHODS—In a cohort of 15,435 women with type 2 diabetes who were members of a health maintenance organization, HbA1c and HRT were assessed by reviewing records in the health plan’s computerized laboratory and pharmacy systems. Sociodemographic and clinical information were collected by survey.

RESULTS—The mean age was 64.7 years (SD ± 8.7). The study cohort comprised 55% non-Hispanic whites, 14% non-Hispanic blacks, 12% Hispanics, 11% Asians, 4% “other” ethnic groups, and 4% with missing ethnicity data. Current HRT was observed in 25% of women. HbA1c levels were significantly lower in women currently using HRT than in women not using HRT (age-adjusted mean ± SE: 7.9 ± 0.03 vs. 8.5 ± 0.02, respectively, P = 0.0001). No differences in HbA1c level were observed between women using unopposed estrogens and women using opposed estrogens. In a Generalized Estimating Equation model, which took into account patient clustering within physician and adjusted for age, ethnicity, education, obesity, hypoglycemic therapy, diabetes duration, self-monitoring of blood glucose, and exercise, HRT remained significantly and independently associated with decreased HbA1c levels (P = 0.0001).

CONCLUSIONS—HRT was independently associated with decreased HbA1c level. Clinical trials will be necessary to understand whether HRT may improve glycemic control in women with diabetes.
Association of the Ala54-thr Polymorphism in the Intestinal Fatty Acid–Binding Protein With 2-h Postchallenge Insulin Levels in the Framingham Offspring Study
Authors: Galluzzi Jennifer R. , Cupples L. Adrienne , Meigs James B. , Wilson Peter W.F. , Schaefer Ernst J. , Ordovas Jose M.
Published: March 2007

OBJECTIVE—To investigate the association of variants of the intestinal fatty acid–binding protein gene (FABP2) with fasting and postchallenge glucose and insulin levels, HbA1c, and prevalence of type 2 diabetes in a separate sample of men and women.

RESEARCH DESIGN AND METHODS—Subjects were participants in the Framingham Offspring Study, a long-term community-based prospective observational study of risk factors for cardiovascular disease. The study sample consisted of 762 men and 922 women.

RESULTS—In women, carriers of the thr54 allele had significantly higher 2-h postchallenge insulin levels than noncarriers (104.4 ± 73.0 vs. 93.4 ± 61.5 μU/ml; P = 0.0139). This relationship remained significant after adjustment for familial relationship, age, BMI, triglycerides, APOE genotype, smoking, alcohol intake, the use of β-blockers, menopausal status, and estrogen therapy. No such significant association was observed in men. In both men and women, there were no statistical associations between the FABP2 polymorphism and BMI, fasting glucose, fasting insulin, 2-h postchallenge glucose levels, HbA1c, and prevalence of type 2 diabetes.

CONCLUSIONS—These results suggest that the FABP2 thr54 allele may have a minor contribution to the insulin resistance syndrome in a white general population.
Association of Physical Activity and Serum Insulin Concentrations in Two Populations at High Risk for Type 2 Diabetes but Differing by BMI
Authors: Kriska Andrea M. , Pereira Mark A. , Hanson Robert L. , de Courten Maximilian P. , Zimmet Paul Z. , Alberti K. George M.M. , Chitson Pierrot , Bennett Peter H. , Narayan K.M. Venkat , Knowler William C.
Published: March 2007

OBJECTIVE—Physical activity and insulin sensitivity are related in epidemiological studies, but the consistency of this finding among populations that greatly differ in body size is uncertain. The present multiethnic epidemiological study examined whether physical activity was related to insulin concentrations in two populations at high risk for diabetes that greatly differ by location, ethnic group, and BMI.

RESEARCH DESIGN AND METHODS—The study populations consisted of 2,321 nondiabetic Pima Indian men and women aged 15–59 years from Arizona and 2,716 nondiabetic men and women aged 35–54 years from Mauritius. Insulin sensitivity was estimated by mean insulin concentration (average of the fasting and postload insulin), and total (i.e., leisure and occupational) physical activity was assessed by questionnaire.

RESULTS—Pima men and women who were more active had significantly (P < 0.05) lower mean insulin concentrations than those less active (BMI and age-adjusted means were 179 vs. 200 and 237 vs. 268 pmol/l). Similar findings were noted in Mauritian men and women (94 vs. 122 and 127 vs. 148 pmol/l). In both populations, activity remained significantly associated with mean insulin concentration controlled for age, BMI, waist-to-thigh or waist-to-hip ratio, and mean glucose concentrations.

CONCLUSIONS—Physical activity was negatively associated with insulin concentrations both in the Pima Indians, who tend to be overweight, and in Mauritians, who are leaner. These findings suggest a beneficial role of activity on insulin sensitivity that is separate from any influence of activity on body composition.
Diminished Insulin Secretory Response to Glucose but Normal Insulin and Glucagon Secretory Responses to Arginine in a Family With Maternally Inherited Diabetes and Deafness Caused by Mitochondrial tRNALEU(UUR) Gene Mutation
Authors: Brändle Michael , Lehmann Roger , Maly Friedrich E. , Schmid Christoph , Spinas Giatgen A.
Published: March 2007

OBJECTIVE—The effects of glucose, arginine, and glucagon on β-cell function as well as α-cell response to arginine were studied in a family with mitochondrial diabetes.

RESEARCH DESIGN AND METHODS—The function of α- and β-cells was assessed in all five siblings carrying the mitochondrial tRNA Leu(UUR) gene mutation at position 3243 and compared with six sex-, age-, and weight-matched control subjects. Insulin and C-peptide responses were evaluated by intravenous glucagon application, intravenous arginine stimulation test, and intravenous glucose tolerance test. Glucagon secretion was assessed during the arginine stimulation test.

RESULTS—The glucose disappearance constant (Kg) value (mean ± SEM 0.61 ± 0.04 vs. 1.1 ± 0.04, P = 0.0002) as well as the acute insulin response to glucose (area under the curve [AUC] 0–10 min, 77.7 ± 50.7 vs. 1,352.3 ± 191.5 pmol/l, P = 0.0004) were decreased in all patients. Similarly, glucagon-stimulated C-peptide response was also impaired (728 ± 111.4 vs. 1,526.7 ± 157.7 pmol/l, P = 0.005), whereas the insulin response to arginine (AUC) was normal (1,346.9 ± 710.8 vs. 1,083.2 ± 132.5 pmol/l, P = 0.699). Acute glucagon response to arginine (AUC) was normal but tended to be higher in the patients than in the control subjects (181.7 ± 47.5 vs. 90.0 ± 21.1 pmol/l, P = 0.099).

CONCLUSIONS—This study shows impaired insulin and C-peptide secretion in response to a glucose challenge and to glucagon stimulation in diabetic patients with mitochondrial tRNA Leu(UUR) gene mutation, although insulin and glucagon secretory responses to arginine were normal.
Long-Term Trends in Childhood Diabetes Mortality: 1968–1998
Authors: DiLiberti John H. , Lorenz Rodney A.
Published: March 2007

OBJECTIVE—In the context of recent improvements in type 1 diabetes therapy, to describe longitudinal trends in mortality attributable to childhood diabetes and to investigate socioeconomic and health services correlates of mortality.

RESEARCH DESIGN AND METHODS—We extracted mortality data for 1968–1998 from National Center for Health Statistics files and covariates from the Bureau of Health Professions Area Resource File. Analytical techniques included linear and Poisson regression and standard descriptive statistics.

RESULTS—Childhood (defined as 0–19 years of age) age-adjusted mortality from diabetes declined from 9.5 (1968) to 3.0 (1984) deaths per 10 million but remained relatively constant subsequently. All-cause childhood mortality, however, continued to decline. Older children experienced higher mortality rates, as did those living in counties with higher levels of unemployment.

CONCLUSIONS—Despite recent improvements in therapy, diabetes-related mortality among children has not declined for 14 years. This finding may be partially attributable to sociodemographic factors influencing access to care, but the remaining mortality may defy available treatment methods. Reducing childhood diabetes mortality rates below the current apparent plateau may require new prevention and/or treatment strategies.
Increased Prevalence of Impaired Glucose Tolerance in Patients With Painful Sensory Neuropathy
Authors: Singleton J. Robinson , Smith A. Gordon , Bromberg Mark B.
Published: March 2007

OBJECTIVE—To characterize a cohort of patients with neuropathy and impaired glucose tolerance (IGT) but no other identifiable cause of neuropathy. Of patients with diabetes, 10% have peripheral neuropathy at the time of their diagnosis, suggesting that axonal injury may occur early in the course of glucose intolerance. The American Diabetes Association (ADA) revised diagnostic criteria to recognize IGT (a serum glucose between 140 and 200 mg/dl in a 2-h oral glucose tolerance test [OGTT]) as a risk factor for cardiovascular disease independent of development of diabetes.

RESEARCH DESIGN AND METHODS—Using revised ADA criteria for diabetes and IGT, we prospectively evaluated 107 sequential patients with idiopathic neuropathy.

RESULTS—A total of 13 of the 107 patients had diabetes, whereas 36 (34%) had IGT, nearly three times the prevalence in age-matched control subjects (P < 0.01). OGTT was often elevated, whereas both fasting plasma glucose and HbA1c were normal. Comparing patients with diabetes, IGT, or normal OGTT, age and BMI were similar. However, painful sensory symptoms were more common in patients with IGT and diabetes, and family history of neuropathy was significantly more common in normoglycemic patients. Electrodiagnostic findings of axonal injury were less severe in patients with IGT and were more likely to be confined to sensory fibers than in patients with diabetes.

CONCLUSIONS—Our results suggest that IGT may cause or contribute to small-fiber neuropathy, which is similar in phenotype to the painful sensory neuropathy commonly encountered in diabetes. Two-hour OGTT is more sensitive than other measures of glucose handling in screening these patients.
Characteristics of an Adult Population With Newly Diagnosed Type 2 Diabetes
Authors: Hillier Teresa A. , Pedula Kathryn L.
Published: March 2007

OBJECTIVE—To determine whether adults diagnosed with type 2 diabetes at 18–44 years of age (early type 2 diabetes) have different metabolic profiles at diagnosis than adults diagnosed at ≥45 years of age (usual type 2 diabetes).

RESEARCH DESIGN AND METHODS—Within a health maintenance organization, we studied characteristics among 2,437 adults newly diagnosed with type 2 diabetes between 1996 and 1998 who had measured weight, HbA1c, blood pressure, and cholesterol within 3 months of diagnosis. We abstracted clinical data from electronic medical records. We compared mean and proportional differences with parametric t tests and χ2 analyses, respectively. We used multiple logistic regression to identify the factors independently associated with the onset group (early vs. usual type 2 diabetes).

RESULTS—There was an inverse linear relationship between BMI and age at diagnosis of type 2 diabetes (P < 0.001). On univariate analysis, adults with early type 2 diabetes were more obese (BMI 39 vs. 33 kg/m2, P < 0.001), were more likely to be female (P = 0.04), had slightly worse glycemic control (HbA1c 7.7 vs. 7.5%, P = 0.03), had a higher prevalence of diastolic hypertension (37 vs. 26%, P < 0.001), despite a lower prevalence of systolic hypertension (34 vs. 55%, P < 0.001), and had an equally high rate of abnormal lipids (82 vs. 78%, P = 0.13) than adults with usual type 2 diabetes. BMI, female gender, cholesterol, and diastolic and systolic blood pressure remained independently associated with onset group at multivariate analysis.

CONCLUSIONS—Although both onset groups were on average obese, the inverse linear relationship of obesity and age of diabetes onset that we observed suggests that obesity is a continuous risk rather than a threshold risk for diabetes onset. Both onset groups had a high prevalence of cardiovascular disease risk factors.
A Biethnic Community Survey of Cognition in Participants With Type 2 Diabetes, Impaired Glucose Tolerance, and Normal Glucose Tolerance
Authors: Lindeman Robert D. , Romero Linda J. , LaRue Asenath , Yau C. Lillian , Schade David S. , Koehler Kathleen M. , Baumgartner Richard N. , Garry Phillip J.
Published: March 2007

OBJECTIVE—To determine whether elderly individuals with type 2 diabetes or impaired glucose tolerance are at increased risk for cognitive impairment compared with individuals with normal glucose tolerance.

RESEARCH DESIGN AND METHODS—Elderly Hispanic individuals (n = 414) and non-Hispanic white individuals (n = 469) aged ≥65 years, randomly selected from the Medicare rolls of Bernalillo County (Albuquerque), NM, were recruited for an interview/examination that included an evaluation of glucose tolerance. Information on nine tests of cognitive function and two measures of depression allowed comparisons between diabetic status and these functions. Comparisons also were made between glycosolated hemoglobin concentrations and these cognitive tests in the 188 participants with diabetes.

RESULTS—None of the mean scores on the tests of cognitive function was significantly lower in the participants with diabetes compared with those participants with normal glucose tolerance after adjustments for ethnicity, sex, age, level of education, and presence of depression, with or without elimination of those with dementia (Mini-Mental State Exam <18). Interestingly, participants with impaired glucose tolerance tended to score higher than those with normal glucose tolerance. No significant associations were found between glycosolated hemoglobin concentrations and cognitive test scores in participants with diabetes.

CONCLUSIONS—We could not show any increased risk for cognitive impairment in participants with diabetes compared with those with normal glucose tolerance after adjustments for ethnicity, sex, age, education, and presence of depression, before or after elimination of dementia in this random sample from a biethnic population of predominantly community-dwelling elders.
Total Antioxidant Status and Coronary Artery Calcification in Type 1 Diabetes
Authors: Valabhji Jonathan , McColl Avril J. , Richmond William , Schachter Michael , Rubens Michael B. , Elkeles Robert S.
Published: March 2007

OBJECTIVE—Type 1 diabetes is associated with a high risk of coronary heart disease (CHD), despite the absence of dyslipidemia. Oxidative modification may render LDLs more atherogenic. We aimed to assess antioxidant status in type 1 diabetes and its association with coronary artery calcification (CAC).

RESEARCH DESIGN AND METHODS—Total antioxidant status (TAS) of serum was measured using the Trolox equivalent antioxidant capacity assay in 48 type 1 diabetic and 25 nondiabetic subjects. The presence of CAC was assessed in the diabetic subjects using electron beam computed tomography.

RESULTS—TAS was reduced in type 1 diabetic subjects compared with nondiabetic subjects (Mann-Whitney U test, P < 0.0001). There were associations between TAS and HbA1c (r = −0.43; P = 0.0026) and duration of diabetes (r = −0.35; P = 0.0157). Significant CAC was considered present if the Agatston score was >10. The diabetic subjects with significant CAC were older (P < 0.0001); had longer duration of diabetes (P = 0.0002); were more likely to have high blood pressure (P = 0.040); had higher total cholesterol concentration (P = 0.039), serum creatinine concentration (P = 0.003), and urinary albumin–to–creatinine ratio (P = 0.022); and had lower serum TAS (P = 0.018) compared with those without significant calcification. In logistic regression with CAC as the dependent variable, TAS was entered as a predictor, and the effects on its predictive value of adding other explanatory variables in bivariate analyses were assessed. The power of TAS to predict CAC was independent of many of the traditional CHD risk factors. Whereas TAS as a predictor was no longer statistically significant when age or duration of diabetes were entered into the model, the odds ratio for a TAS concentration above the median value predicting significant CAC only increased from 0.19 to 0.26 and 0.32, respectively.

CONCLUSIONS—TAS is reduced in type 1 diabetes and is associated with the presence of CAC.
Impaired Incretin Response After a Mixed Meal Is Associated With Insulin Resistance in Nondiabetic Men
Authors: Rask Eva , Olsson Tommy , Söderberg Stefan , Johnson Owe , Seckl Jonathan , Holst Jens Juul , Ahrén Bo
Published: March 2007

OBJECTIVE—To investigate whether features of the insulin resistance syndrome are associated with altered incretin responses to food intake.

RESEARCH DESIGN AND METHODS—From a population-based study, 35 men were recruited, representing a wide spectrum of insulin sensitivity and body weight. Each subject underwent a hyperinsulinemic-euglycemic clamp to determine insulin sensitivity. A mixed meal was given, and plasma levels of gastric inhibitory polypeptide (GIP) and glucagon-like peptide 1 (GLP-1), as well as insulin, glucagon, and glucose were measured.

RESULTS—Insulin resistance was associated with impaired GIP and GLP-1 responses to a mixed meal. The total area under the curve (AUC) of the GIP response after the mixed meal was associated with insulin sensitivity (r = 0.54, P < 0.01). There was a significant difference between the highest and the lowest tertile of insulin sensitivity (P < 0.05). GLP-1 levels 15 min after food intake were significantly lower in the most insulin-resistant tertile compared with the most insulin-sensitive tertile. During the first hour, the AUC of GLP-1 correlated significantly with insulin sensitivity (r = 0.47, P < 0.01). Multiple linear regression analysis showed that insulin resistance, but not obesity, was an independent predictor of these decreased incretin responses.

CONCLUSIONS—In insulin resistance, the GIP and GLP-1 responses to a mixed meal are impaired and are related to the degree of insulin resistance. Decreased incretin responsiveness may be of importance for the development of impaired glucose tolerance.
Carriers of an Inactivating β-Cell ATP-Sensitive K+ Channel Mutation Have Normal Glucose Tolerance and Insulin Sensitivity and Appropriate Insulin Secretion
Authors: Huopio Hanna , Vauhkonen Ilkka , Komulainen Jorma , Niskanen Leo , Otonkoski Timo , Laakso Markku
Published: March 2007

OBJECTIVE—Insulin release from the pancreatic β-cells is controlled by ATP-sensitive K+ (KATP) channels, which consist of a hetero-octameric complex of four sulfonylurea receptor 1 (SUR1) and four Kir6.2 proteins. Mutations in the SUR1 gene are the major cause of congenital hyperinsulinemia (CHI). Despite the hereditary nature of CHI, studies of glucose homeostasis in heterozygous relatives of CHI patients are lacking. Theoretically, in the heterozygous state of the SUR1 gene mutation, only 1 of 16 KATP channels consists of entirely normal subunits. The aim of our study was to investigate in vivo the glucose homeostasis of heterozygous SUR1 mutation carriers.

RESEARCH DESIGN AND METHODS—We studied 8 parents of CHI patients, all 8 of whom were heterozygous for the inactivating SUR1 mutation V187D, and 10 matched control subjects. We evaluated glucose tolerance and insulin secretory capacity with oral and intravenous glucose tests, rates of whole-body glucose uptake with hyperinsulinemic-euglycemic clamps, C-peptide response to hypoglycemia during hyperinsulinemic-hypoglycemic clamp, and function of the KATP channels with intravenous tolbutamide test.

RESULTS—Carriers of the V187D substitution had normal glucose tolerance, normal tissue sensitivity to insulin, and no signs of inappropriate insulin secretion. The normal insulin response to tolbutamide indicated that heterozygosity for the V187D mutation did not impair KATP channel function.

CONCLUSIONS—We conclude that the heterozygous carriers of the SUR1 mutation had normal glucose metabolism and insulin secretion, indicating that carriers of recessive KATP channel mutations are unlikely to be at an increased risk of hypoglycemia or other disturbances in glucose metabolism.
Long-Term Impact of Neonatal Breast-Feeding on Body Weight and Glucose Tolerance in Children of Diabetic Mothers
Authors: Plagemann Andreas , Harder Thomas , Franke Kerstin , Kohlhoff Rainer
Published: March 2007

OBJECTIVE—Offspring born to women with pregnancies complicated by diabetes are at increased childhood risk of developing obesity and impaired glucose tolerance (IGT). In population-based studies, breast-feeding has been shown to be protective against obesity and diabetes later in life. To date, the role of breast-feeding on offspring of diabetic mothers (ODM) has not been investigated in this context.

RESEARCH DESIGN AND METHODS—A total of 112 ODM (type 1 diabetes, n = 83; gestational diabetes, n = 29) were evaluated prospectively for impact of ingestion of either diabetic breast milk (DBM) or nondiabetic banked donor breast milk (BBM) during the early neonatal period (day 1–7 of life) on relative body weight and glucose tolerance at a mean age of 2 years.

RESULTS—There was a positive correlation between the volume of DBM ingested and risk of overweight at 2 years of age (odds ratio [OR] 2.47, 95% CI 1.25–4.87). In contrast, the volume of BBM ingested was inversely correlated to body weight at follow-up (P = 0.001). Risk of childhood IGT decreased by increasing amounts of BBM ingested neonatally (OR 0.19, 95% CI 0.05–0.70). Stepwise regression analysis showed volume of DBM to be the only significant predictor of relative body weight at 2 years of age (P = 0.001).

CONCLUSIONS—Early neonatal ingestion of breast milk from diabetic mothers may increase risk of becoming overweight and, consequently, developing IGT during childhood. Additional studies are needed to assess long-term consequences that might result from the type of neonatal nutrition in ODM.
Impact of Computer-Generated Personalized Goals on HbA1c
Authors: Levetan Claresa S. , Dawn Karen R. , Robbins David C. , Ratner Robert E.
Published: March 2007

OBJECTIVE—The public is increasingly aware of the importance of HbA1c testing, yet the vast majority of patients with diabetes do not know their HbA1c status or goal. We set forth to evaluate the impact of a system that provides uniquely formatted and personalized reports of diabetes status and goals on changes in HbA1c levels.

RESEARCH DESIGN AND METHODS—A total of 150 patients with diabetes were randomized to receive either standard care or intervention inclusive of a computer-generated 11” × 17” color poster depicting an individual’s HbA1c status and goals along with personalized steps to aid in goal achievement. All patients enrolled received diabetes education during the 3 months before enrollment. HbA1c was performed at baseline and 6 months.

RESULTS—At baseline, there were no significant differences between patient groups in terms of age, sex, education level, race, and HbA1c or lipid levels. Among patients with baseline HbA1c ≥7.0%, there was an 8.6% (0.77% absolute) reduction in HbA1c among control subjects compared with a 17.0% (1.69% absolute) decline in the intervention group (P = 0.032). There were no differences between the control and intervention groups with respect to the frequency of patients experiencing any decline in HbA1c (63 vs. 69%, P = 0.87); among these patients experiencing a decline, the most substantial reductions were seen with the control group, which had a 13.3% (1.15% absolute) decline compared with the intervention patients, who reduced their HbA1c by 24.2% (2.26% absolute reduction; P = 0.0048). At study close, 77% of the patients had their poster displayed on their refrigerator.

CONCLUSIONS—This unique and personalized computer-generated intervention resulted in HbA1c lowering comparable to that of hypoglycemic agents.