bluuebunny/crossref_metadata_2025 huggingface dataset:
Skeletal Muscle Triglyceride
Authors: Kelley David E. , Goodpaster Bret H.
Published: March 2007

Recent evidence derived from four independent methods indicates that an excess triglyceride storage within skeletal muscle is linked to insulin resistance. Potential mechanisms for this association include apparent defects in fatty acid metabolism that are centered at the mitochondria in obesity and in type 2 diabetes. Specifically, defects in the pathways for fatty acid oxidation during postabsorptive conditions are prominent, leading to diminished use of fatty acids and increased esterification and storage of lipid within skeletal muscle. These impairments in fatty acid metabolism during fasting conditions may be related to a metabolic inflexibility in insulin resistance that is not limited to defects in glucose metabolism during insulin-stimulated conditions. Thus, there is substantial evidence implicating perturbations in fatty acid metabolism during accumulation of skeletal muscle triglyceride and in the pathogenesis of insulin resistance. Weight loss by caloric restriction improves insulin sensitivity, but the effects on fatty acid metabolism are less conspicuous. Nevertheless, weight loss decreases the content of triglyceride within skeletal muscle, perhaps contributing to the improvement in insulin action with weight loss. Alterations in skeletal muscle substrate metabolism provide insight into the link between skeletal muscle triglyceride accumulation and insulin resistance, and they may lead to more appropriate therapies to improve glucose and fatty acid metabolism in obesity and in type 2 diabetes.
Effect of Mild Exercise Training on Glucose Effectiveness in Healthy Men
Authors: Nishida Yuichiro , Higaki Yasuki , Tokuyama Kumpei , Fujimi Kanta , Kiyonaga Akira , Shindo Munehiro , Sato Yuzo , Tanaka Hiroaki
Published: March 2007

OBJECTIVE—To detect whether mild exercise training improves glucose effectiveness (SG), which is the ability of hyperglycemia to promote glucose disposal at basal insulin, in healthy men.

RESEARCH DESIGN AND METHODS—Eight healthy men (18–25 years of age) underwent ergometer training at lactate threshold (LT) intensity for 60 min/day for 5 days/week for 6 weeks. An insulin-modified intravenous glucose tolerance test was performed before as well as at 16 h and 1 week after the last training session. SG and insulin sensitivity (SI) were estimated using a minimal-model approach.

RESULTS—After the exercise training, Vo2max and Vo2 at LT increased by 5 and 34%, respectively (P < 0.05). The mild exercise training improves SG measured 16 h after the last training session, from 0.018 ± 0.002 to 0.024 ± 0.001 min−1 (P < 0.05). The elevated SG after exercise training tends to be maintained regardless of detraining for 1 week (0.023 ± 0.002 min−1, P = 0.09). SI measured at 16 h after the last training session significantly increased (pre-exercise training, 13.9 ± 2.2; 16 h, 18.3 ± 2.4, ×10−5 · min−1 · pmol/l−1, P < 0.05) and still remained elevated 1 week after stopping the training regimen (18.6 ± 2.2, ×10−5 · min−1 · pmol/l−1, P < 0.05).

CONCLUSIONS—Mild exercise training at LT improves SG in healthy men with no change in the body composition. Improving not only SI but also SG through mild exercise training is thus considered to be an effective method for preventing glucose intolerance.
Lipid and Blood Pressure Treatment Goals for Type 1 Diabetes
Authors: Orchard Trevor J. , Forrest Kimberly Y.-Z. , Kuller Lewis H. , Becker Dorothy J.
Published: March 2007

OBJECTIVE—Subjects with type 1 diabetes are at high risk for many long-term complications, including early mortality and coronary artery disease (CAD). Few data are available on which to base goal levels for two major risk factors, namely blood pressure and lipid/lipoproteins. The objective of this study was to determine at which levels of LDL and HDL cholesterol, triglycerides, and blood pressure the relative risks of type 1 diabetic complications increase significantly.

RESEARCH DESIGN AND METHODS—Observational prospective study of 589 patients with childhood-onset type 1 diabetes (<17 years) aged ≥18 years at baseline; 10-year incidence of mortality, CAD, lower-extremity arterial disease, proliferative retinopathy, distal symmetric polyneuropathy, and overt nephropathy. Relative risks were determined using traditional groupings of blood pressure and lipid/lipoproteins, measured at baseline, using the lowest groupings (<100 mg/dl [2.6 mmol/l] LDL cholesterol, <45 mg/dl [1.1 mmol/l] HDL cholesterol, <100 mg/dl [1.1 mmol/l] triglycerides, <110 mmHg systolic blood pressure, and <80 mmHg diastolic blood pressure) as reference. Adjustments for age, sex, and glycemic control were examined.

RESULTS—Driven mainly by strong relationships (RR range 1.8–12.1) with mortality, CAD, and overt nephropathy, suggested goal levels are as follows: LDL cholesterol <100 mg/dl (2.6 mmol/l), HDL cholesterol >45 mg/dl (1.1 mmol/l), triglycerides <150 mg/dl (1.7 mmol/l), systolic blood pressure <120 mmHg, and diastolic blood pressure <80 mmHg. Age, sex, and glycemic control had little influence on these goals.

CONCLUSIONS—Although observational in nature, these data strongly support the case for vigorous control of lipid levels and blood pressure in patients with type 1 diabetes.
A Systematic Approach to Risk Stratification and Intervention Within a Managed Care Environment Improves Diabetes Outcomes and Patient Satisfaction
Authors: Clark Charles M. , Snyder James W. , Meek Robert L. , Stutz Linda M. , Parkin Christopher G.
Published: March 2007

OBJECTIVE—To determine whether a comprehensive diabetes management program that included risk stratification and social marketing would improve clinical outcomes and patient satisfaction within a managed care organization (MCO).

RESEARCH DESIGN AND METHODS—The 12-month prospective trial was conducted at primary care clinics within a MCO and involved 370 adults with diabetes. Measurements included 1) the frequency of dilated eye and foot examinations, microalbuminuria assessment, blood pressure measurement, lipid profile, and HbA1c measurement; 2) changes in blood pressure, lipid levels, and HbA1c levels; and 3) changes in patient satisfaction.

RESULTS—Complete data are reported for the 193 patients who had been enrolled for 12 months; life table analysis is reported for all patients who remained enrolled at the study’s end as well as for a comparative control group of 623 patients. For the 193 patients for whom 12-month data were available, the number of patients in the low-risk category (HbA1c <7%) increased by 51.1%. A total of 97.4% of patients with an HbA1c >8% at baseline had a change in treatment regimen. Patients at the highest risk for coronary heart disease (LDL >130 mg/dl) decreased from 25.4% at baseline to 20.2%. Patients with a blood pressure <130/85 mmHg increased from 23.8 to 44.6%. Of these patients, 63.0% had changes in medication. Patients and providers expressed significant increases in satisfaction with the program.

CONCLUSIONS—The program was successful in initiating the recommended changes in the diabetic therapeutic regimen, resulting in improved glycemic control, increased monitoring/management of diabetic complications, and greater patient and provider satisfaction. These results should have great significance in the design of future programs in MCOs aimed at improving the care of people with diabetes and other chronic diseases.
The Relationship of Fasting Plasma Glucose Values and Other Variables to 2-h Postload Plasma Glucose in Japanese Subjects
Authors: Bando Yukihiro , Ushiogi Yasuyuki , Okafuji Kazuhiro , Toya Daisyu , Tanaka Nobuyoshi , Fujisawa Masakiyo
Published: March 2007

OBJECTIVE—To investigate the relationship between fasting plasma glucose (FPG) values and other variables (e.g., age, sex, and BMI) to 2-h post–75-g oral glucose load glycemia (PG) in Japanese subjects.

RESEARCH DESIGN AND METHODS—Subjects included 13,694 Japanese subjects between 20 and 83 years of age (10,677 men and 3,017 women) who were undergoing a 75-g oral glucose tolerance test (OGTT) during a health screening performed at our hospital. The influences of age for 2-h PG at a fixed fasting plasma glucose (FPG) level of 126 mg/dl were analyzed. Multiple linear regression analysis was performed using a model in which the dependent variable was 2-h PG using the following explanatory variables: FPG, age, sex, BMI, blood pressure, plasma cholesterol, and triglyceride (TG) levels.

RESULTS—The 2-h PG at a fixed FPG of 126 mg/dl increased by 0.94 mg/dl per year in patients aged between 30 and 78 years (r = 0.68, P < 0.0001). In multiple regression, five explanatory variables (FPG, age, BMI, plasma TG levels, and systolic blood pressure levels) were all positively associated with 2-h PG. The percentages of patients with 2-h diabetes (isolated postchallenge hyperglycemia [IPH]) versus fasting plus 2-h diabetes by the World Health Organization criteria significantly (P = 0.005) increased as the patients’ decades increased, whereas the impact of BMI on the percentages was significant only in young patients (P = 0.001).

CONCLUSIONS—Aging was found to be the second best predictor of 2-h PG on multiple regression. Therefore, OGTT should be performed especially in elderly patients because they show IPH more frequently.
Diabetes and Risk of Fracture
Authors: Ivers Rebecca Q. , Cumming Robert G. , Mitchell Paul , Peduto Anthony J.
Published: March 2007

OBJECTIVE—To examine associations between measures of diabetes and risk of fracture in a population-based sample of older Australians.

RESEARCH DESIGN AND METHODS—This was a prospective study of 3,654 subjects aged 49 years and older who were residents in the Blue Mountains, west of Sydney, Australia. At baseline, subjects were asked questions about history and treatment of diabetes, and fasting blood samples were taken. Photographs were taken of the retina and lens to grade retinopathy and cataract. Details of fractures (excluding rib and vertebral fractures) were collected by a combination of self-report and medical record searches; all fractures were radiologically confirmed.

RESULTS—After 2 years of follow-up, we found that several diabetes-related factors were significantly associated (in multivariate models) with increased risk of all fractures combined, including presence of diabetic retinopathy (adjusted RR 5.4, 95% CI 2.7–10.8), diabetes duration ≥10 years (3.3, 1.3–8.2), cortical cataract involving ≥25% of the lens area (2.5, 1.3–4.7), and insulin treatment (5.9, 2.6–13.5). The proximal humerus was the only individual fracture site associated with diabetes. Diabetic retinopathy (10.3, 2.2–48.0), diabetes duration (for ≥10 years duration; 11.4, 2.4–54.2), and insulin treatment (18.8, 4.0–88.7) were all associated with proximal humerus fracture.

CONCLUSIONS—These data suggest a significantly increased risk of fracture associated with diabetic retinopathy, advanced cortical cataract, longer diabetes duration, and insulin treatment. However, there are some shortcomings in this study that may limit these findings.
Cross-Sectional and Prospective Associations Between Proinsulin and Cardiovascular Disease Risk Factors in a Population Experiencing Rapid Cultural Transition
Authors: Hanley Anthony J.G. , McKeown-Eyssen Gail , Harris Stewart B. , Hegele Robert A. , Wolever Thomas M.S. , Kwan Jeremy , Connelly Philip W. , Zinman Bernard
Published: March 2007

OBJECTIVE—To examine cross-sectional and prospective associations between proinsulin and cardiovascular disease risk factors using data from a population-based study of type 2 diabetes among Native Canadians.

RESEARCH DESIGN AND METHODS—Between 1993 and 1995, 72% of eligible members of a Native Canadian community participated in a baseline diabetes prevalence survey. Fasting samples were collected for glucose, C-peptide, proinsulin, lipids, and apolipoproteins. A 75-g oral glucose tolerance test was administered, and a second sample for glucose was drawn after 120 min. Blood pressure and waist circumference were determined. In the present study, subjects with normal glucose tolerance (NGT) (n = 505) and impaired glucose tolerance (IGT) (n = 74) were included in cross-sectional analyses. In 1998, 95 individuals who had IGT or NGT at baseline with an elevated 2-h glucose concentration (≥7.0 mmol/l) participated in a follow-up evaluation using the protocol used at baseline. Cross-sectional and prospective associations between proinsulin and cardiovascular risk factors were assessed using correlation and multiple linear regression analyses.

RESULTS—After adjustment for covariates including age, sex, C-peptide, waist circumference, and glucose tolerance status, fasting proinsulin concentration was significantly associated with concurrently measured lipid and apolipoprotein concentrations (triglycerides: r = 0.18, P < 0.0001; total cholesterol: r = 0.10, P = 0.02; LDL cholesterol: r = 0.11, P = 0.01; HDL cholesterol: r = −0.16, P = 0.0002; apolipoprotein (apo) B: r = 0.17, P < 0.0001; apoAI: r = −0.11, P = 0.008). In the adjusted prospective analysis, baseline triglycerides, HDL cholesterol, and apoB were associated with changes over time in proinsulin (r = 0.23, P = 0.04; r = −0.30, P = 0.01; r = 0.23, P = 0.04; respectively).

CONCLUSIONS—These results confirm previously reported cross-sectional associations between proinsulin and lipid concentrations. In addition, an unexpected association between baseline lipids and proinsulin change was documented.
Third-Trimester Maternal Glucose Levels From Diurnal Profiles in Nondiabetic Pregnancies
Authors: Parretti Elena , Mecacci Federico , Papini Marta , Cioni Riccardo , Carignani Lucia , Mignosa Marcella , La Torre Pasquale , Mello Giorgio
Published: March 2007

OBJECTIVE—To assess the 24-h glucose levels in a group of nondiabetic, nonobese pregnant women and to verify the presence of correlations between maternal glucose levels and sonographic parameters of fetal growth.

RESEARCH DESIGN AND METHODS—A total of 66 Caucasian nonobese pregnant women with normal glucose challenge tests (GCT) enrolled in the study; from this population, we selected 51 women who delivered term (from 37 to 42 weeks completed) live-born infants without evidence of congenital malformations. The women were requested to have three main meals and to perform daily glucose profiles fortnightly from 28–38 weeks without modifying their lifestyle or following any dietary restriction. All subjects were taught how to monitor their blood glucose by using a reflectance meter. Fetal biometry was evaluated by ultrasound scan according to standard methodology at 22, 28, 32, and 36 weeks of pregnancy.

RESULTS—The overall daily mean glucose level during the third trimester was 74.7 ± 5.2 mg/dl. Daily mean glucose values increased between 28 (71.9 ± 5.7 mg/dl) and 38 (78.3 ± 5.4 mg/dl) weeks of pregnancy. We found a significant positive correlation at 28 weeks between 1-h postprandial glucose values and fetal abdominal circumference (AC). At 32 weeks, we documented positive correlations between fetal AC and maternal blood glucose levels 1 h after breakfast, 1 and 2 h after lunch, and 1 and 2 h after dinner. At 36 weeks, there was a positive correlation between fetal AC and 1- and 2-h postprandial blood glucose levels. In addition, there was a negative correlation between head-abdominal circumference ratio and 1-h postprandial blood glucose values.

CONCLUSIONS—This longitudinal study first provides a contribution toward the definition of normoglycemia in nondiabetic, nonobese pregnant women; moreover, it reveals significant correlations of postprandial blood glucose levels with the growth of insulin-sensitive fetal tissues and, in particular, between 1-h postprandial blood glucose values and fetal AC.
The Diabetes Network Internet-Based Physical Activity Intervention
Authors: McKay H. Garth , King Diane , Eakin Elizabeth G. , Seeley John R. , Glasgow Russell E.
Published: March 2007

OBJECTIVE—Because of other competing priorities, physical activity (PA) is seldom addressed in a consistent way in either primary care or diabetes education . This 8-week pilot study evaluated the short-term benefits of an Internet-based supplement to usual care that focused on providing support for sedentary patients with type 2 diabetes to increase their PA levels.

RESEARCH DESIGN AND METHODS—A total of 78 type 2 diabetic patients (53% female, average age 52.3 years) were randomized to the Diabetes Network (D-Net) Active Lives PA Intervention or an Internet information-only condition. The intervention condition received goal-setting and personalized feedback, identified and developed strategies to overcome barriers, received and could post messages to an on-line “personal coach,” and were invited to participate in peer group support areas. Key outcomes included minutes of PA per week and depressive symptomatology.

RESULTS—There was an overall moderate improvement in PA levels within both intervention and control conditions, but there was no significant improvement in regard to condition effects. There was substantial variability in both site use and outcomes within the intervention and control conditions. Internal analyses revealed that among intervention participants, those who used the site more regularly derived significantly greater benefits, whereas those in the control condition derived no similar benefits with increased program use.

CONCLUSIONS—Internet-based self-management interventions for PA and other regimen areas have great potential to enhance the care of diabetes and other chronic conditions. We conclude that greater attention should be focused on methods to sustain involvement with Internet-based intervention health promotion programs over time.
Persistent Differences Among Centers Over 3 Years in Glycemic Control and Hypoglycemia in a Study of 3,805 Children and Adolescents With Type 1 Diabetes From the Hvidøre Study Group
Authors: Danne Thomas , Mortensen Henrik B. , Hougaard Philip , Lynggaard Helle , Aanstoot Henk-Jan , Chiarelli Francesco , Daneman Denis , Dorchy Harry , Garandeau Patrick , Greene Stephen A. , Hoey Hilary , Holl Reinhard W. , Kaprio Eero A. , Kocova Mirjana , Martul Pedro , Matsuura Nobuo , Robertson Kenneth J. , Schoenle Eugen J. , Søvik Oddmund , Swift Peter G.F. , Tsou Rosa M. , Vanelli Maurizio , Åman Jan ,   for the Hvidøre Study Group on Childhood Diabetes
Published: March 2007

OBJECTIVE—Twenty-one international pediatric diabetes centers from 17 countries investigated the effect of simple feedback about the grand mean HbA1c level of all centers and the average value of each center on changes in metabolic control, rate of severe hypoglycemia, and insulin therapy over a 3-year period.

RESEARCH DESIGN AND METHODS—Clinical data collection and determination of HbA1c levels were conducted at a central location in 1995 (n = 2,780, age 0–18 years) and 1998 (n = 2,101, age 11–18 years).

RESULTS—Striking differences in average HbA1c concentrations were found among centers; these differences remained after adjustment for the significant confounders of sex, age, and diabetes duration. They were apparent even in patients with short diabetes duration and remained stable 3 years later (mean adjusted HbA1c level: 8.62 ± 0.03 vs. 8.67 ± 0.04 [1995 vs. 1998, respectively]). Three centers had improved significantly, four centers had deteriorated significantly in their overall adjusted HbA1c levels, and 14 centers had not changed in glycemic control. During the observation period, there were increases in the adjusted insulin dose by 0.076 U/kg, the adjusted number of injections by 0.23 injections per day, and the adjusted BMI by 0.95 kg/m2. The 1995 versus 1998 difference in glycemic control for the seven centers could not be explained by prevailing insulin regimens or rates of hypoglycemia.

CONCLUSIONS—This study reveals significant outcome differences among large international pediatric diabetes centers. Feedback and comparison of HbA1c levels led to an intensification of insulin therapy in most centers, but improved glycemic control in only a few.
Evaluation of the Insulin Resistance Syndrome in 5- to 10-Year-Old Overweight/Obese African-American Children
Authors: Young-Hyman Deborah , Schlundt David G. , Herman Leanna , De Luca Francesco , Counts Debra
Published: March 2007

OBJECTIVE—To characterize the insulin sensitivity of overweight and obese 5- to 10-year-old (Tanner stage 1–3) African-American children screened for participation in a diabetes prevention study and to identify the association of insulin sensitivity with obesity, hyperlipidemia, and hypertension.

RESEARCH DESIGN AND METHODS—Measures of insulin resistance (homeostasis model assessment) and insulin sensitivity (Matsuda and DeFronzo’s whole-body insulin sensitivity) were calculated from a 2-h oral glucose tolerance test in 137 African-American children recruited into a diabetes prevention study. Measures of lipids (LDL, HDL, total cholesterol, and triglycerides), blood pressure, and body composition were obtained for a subset of the children.

RESULTS—In response to a glucose challenge, girls and older and heavier children produced significantly more insulin. As BMI increased, there was a statistically significant decrease in insulin sensitivity, particularly in girls. Insulin sensitivity was inversely correlated with increases in blood pressure, triglycerides, subcutaneous fat, the percentage of total body fat, and Tanner stage, but it was not correlated with LDL and HDL.

CONCLUSIONS—Reduced insulin sensitivity and the cluster of risk factors known as the insulin resistance syndrome (IRS) are already apparent in these overweight African-American children. Young African-American girls, in particular, already show evidence of hyperinsulinemia in response to a glucose load, suggesting that the early stages of metabolic decompensation that lead to type 2 diabetes are already occurring. Monitoring of those risk factors known to be part of IRS should become part of routine medical care for overweight or obese African-American children.
Fasting Plasma Homocysteine Levels in the Insulin Resistance Syndrome
Authors: Meigs James B. , Jacques Paul F. , Selhub Jacob , Singer Daniel E. , Nathan David M. , Rifai Nader , D’Agostino Ralph B. , Wilson Peter W.F.
Published: March 2007

OBJECTIVE—Insulin resistance, associated metabolic abnormalities, and elevated homocysteine levels are risk factors for cardiovascular disease (CVD). We examined relationships between homocysteine levels and features of insulin resistance syndrome (IRS).

RESEARCH DESIGN AND METHODS—We measured clinical characteristics, plasma levels of fasting homocysteine, folate, B vitamins, creatinine, and fasting and 2-h insulin and glucose levels after a 75-g oral glucose tolerance test in 2,214 subjects without CVD at the fifth examination (1991–1995) of the Framingham Offspring Study. After excluding 203 subjects with diabetes, the remaining 2,011 subjects were categorized as having none, one, two, or all three of the phenotypes of IRS: impaired glucose tolerance, hypertension, and/or a central metabolic syndrome (two or more traits: obesity, dyslipidemia, or hyperinsulinemia). In addition, in 1,592 subjects attending the sixth examination (1995–1998), we measured the urine albumin/creatinine ratio (UACR). Age-, sex-, creatinine-, vitamin-, and UACR-adjusted mean homocysteine levels or proportions with homocysteine >14 μmol/l in each phenotypic category and differences between categories were assessed with regression models.

RESULTS—The mean age of the subjects was 54 years (range 28–82); 55% were women, 12.3% had hyperinsulinemia, and 15.9% had two or more of the IRS phenotypes. Adjusted mean homocysteine levels were higher comparing those with hyperinsulinemia (9.8 μmol/l) and those without (9.4 μmol/l, P = 0.04) and were higher among subjects with two or more IRS phenotypes (9.9 μmol/l) compared with those with 1 or no phenotype (9.3 μmol/l, P = 0.003). Mean UACR levels were also higher among subjects with two or more IRS phenotypes (7.2 mg/g) compared with those with 1 or no phenotype (5.5 mg/g, P = 0.007).

CONCLUSIONS—Hyperhomocysteinemia and abnormal urinary albumin excretion are both associated with hyperinsulinemia and may partially account for increased risk of CVD associated with insulin resistance. Because hyperhomocysteinemia and microalbuminuria also reflect endothelial injury, these observations also support the hypothesis that endothelial dysfunction is associated with expression of the IRS.
Impact of Diabetes on Long-Term Survival After Acute Myocardial Infarction
Authors: Mukamal Kenneth J. , Nesto Richard W. , Cohen Mylan C. , Muller James E. , Maclure Malcolm , Sherwood Jane B. , Mittleman Murray A.
Published: March 2007

OBJECTIVE—To determine the effect of diabetes on long-term survival after acute myocardial infarction and to compare its effect with that of a previous myocardial infarction.

RESEARCH DESIGN AND METHODS—In a prospective cohort study, we followed 1,935 patients hospitalized with a confirmed acute myocardial infarction at 45 U.S. medical centers between 1989 and 1993, as part of the Determinants of Myocardial Infarction Onset Study. Trained interviewers performed chart reviews and face-to-face interviews with all patients. We analyzed survival using Cox proportional hazards regression to control for potentially confounding factors.

RESULTS—Of the 1,935 patients, 320 (17%) died during a mean follow-up of 3.7 years. A total of 399 patients (21%) had previously diagnosed diabetes. Diabetes was associated with markedly higher total mortality in unadjusted (hazard ratio [HR] 2.4; 95% CI 1.9–3.0) and adjusted (1.7; 1.3–2.1) analyses. The magnitude of the effect of diabetes was identical to that of a previous myocardial infarction. The effect of diabetes was not significantly modified by age, smoking, household income, use of thrombolytic therapy, type of hypoglycemic treatment, or duration of diabetes, but the risk associated with diabetes was higher among women than men (adjusted HRs 2.7 vs. 1.3, P = 0.01).

CONCLUSIONS—Diabetes is associated with markedly increased mortality after acute myocardial infarction, particularly in women. The increase in risk is of the same magnitude as a previous myocardial infarction and provides further support for aggressive treatment of coronary risk factors among diabetic patients.
Dermal Neurovascular Dysfunction in Type 2 Diabetes
Authors: Vinik Aaron I. , Erbas Tomris , Park Tae Sun , Stansberry Kevin B. , Scanelli John A. , Pittenger Gary L.
Published: March 2007

OBJECTIVE—To review evidence for a relationship between dermal neurovascular dysfunction and other components of the metabolic syndrome of type 2 diabetes.

RESEARCH DESIGN AND METHODS—We review and present data supporting concepts relating dermal neurovascular function to prediabetes and the metabolic syndrome. Skin blood flow can be easily measured by laser Doppler techniques.

RESULTS—Heat and gravity have been shown to have specific neural, nitrergic, and independent mediators to regulate skin blood flow. We describe data showing that this new tool identifies dermal neurovascular dysfunction in the majority of type 2 diabetic patients. The defect in skin vasodilation is detectable before the development of diabetes and is partially correctable with insulin sensitizers. This defect is associated with C-fiber dysfunction (i.e., the dermal neurovascular unit) and coexists with variables of the insulin resistance syndrome. The defect most likely results from an imbalance among the endogenous vasodilator compound nitric oxide, the vasodilator neuropeptides substance P and calcitonin gene-related peptide, and the vasoconstrictors angiotensin II and endothelin. Hypertension per se increases skin vasodilation and does not impair the responses to gravity, which is opposite to that of diabetes, suggesting that the effects of diabetes override and counteract those of hypertension.

CONCLUSIONS—These observations suggest that dermal neurovascular function is largely regulated by peripheral C-fiber neurons and that dysregulation may be a component of the metabolic syndrome associated with type 2 diabetes.
Does Microalbuminuria Predict Diabetic Nephropathy?
Authors: Tabaei Bahman P. , Al-Kassab Abdul S. , Ilag Liza L. , Zawacki Catherine M. , Herman William H.
Published: March 2007

OBJECTIVE—To describe risk factors associated with microalbuminuria (MA) in subjects with diabetes, investigate the predictive value of MA as a marker of risk for diabetic nephropathy (DN), and define risk factors associated with the development and progression of MA.

RESEARCH DESIGN AND METHODS—We conducted a prospective longitudinal study of 23 diabetic subjects with persistent MA and 209 diabetic subjects without MA who attended diabetes clinics at the University of Michigan Medical Center in 1989 and 1990. Both groups were examined at baseline and after 7 years. At baseline, urinary albumin–to–creatinine ratios were studied in random, first morning, and 24-h urine samples. At follow-up, a 12-h overnight urine sample was collected and analyzed for albumin and creatinine. At baseline, MA was defined by at least two separate urine specimens with albumin–to–creatinine ratios between 30 and 299 μg albumin per milligram of creatinine.

RESULTS—MA regressed in 56% of subjects with baseline MA without systematic application of corrective measures and developed in 16% of subjects without baseline MA. The predictive value positive of MA as a marker of risk for DN was 43%, and the predictive value negative was 77%. In the combined cohort, the incidence and progression of MA were significantly associated with poor glycemic control and duration of diabetes between 10 and 14 years.

CONCLUSIONS—MA may not be as sensitive and specific a predictor of DN as previously suggested. Other markers of risk for DN are needed for optimal clinical management.
Clinically Useful Estimates of Insulin Sensitivity During Pregnancy
Authors: Kirwan John P. , Huston-Presley Larraine , Kalhan Satish C. , Catalano Patrick M.
Published: March 2007

OBJECTIVE—We examined whether selected indexes of insulin sensitivity derived from an oral glucose tolerance test (ISOGTT) or fasting glucose/insulin levels (ISQUICKI and ISHOMA) can be used to predict insulin sensitivity in women before and during pregnancy.

RESEARCH DESIGN AND METHODS—A 2-h euglycemic-hyperinsulinemic clamp (5 mmol/l glucose, 40 mU · m−2 · min−1 insulin) and a 120-min oral glucose tolerance test (75 g load pregravid, 100 g pregnant) were repeated on 15 women (10 with normal glucose tolerance [NGT] and 5 with gestational diabetes mellitus [GDM]) pregravid and during both early (12–14 weeks) and late (34–36 weeks) pregnancy. An index of insulin sensitivity derived from the clamp (ISCLAMP) was obtained from glucose infusion rates adjusted for change in fat-free mass and endogenous glucose production measured using [6,6-2H2]glucose.

RESULTS—Univariate analysis using combined groups and periods of pregnancy resulted in significant correlations between ISCLAMP and ISOGTT (r2 = 0.74, P < 0.0001), ISQUICKI (r2 = 0.64, P < 0.0001), and ISHOMA (r2 = 0.53, P < 0.0001). The ISOGTT provided a significantly better correlation (P < 0.0001) than either ISQUICKI or ISHOMA. Multivariate analysis showed a significant group effect (P < 0.0003) on the prediction model, and separate equations were developed for the NGT (r2 = 0.64, P < 0.0001) and GDM (r2 = 0.85, P < 0.0001) groups. When subdivided by period of pregnancy, the correlation between ISCLAMP and ISOGTT pregravid was r2 = 0.63 (P = 0.0002), during early pregnancy was r2 = 0.80 (P < 0.0001), and during late pregnancy was r2 = 0.64 (P = 0.0002).

CONCLUSIONS—Estimates of insulin sensitivity from the ISOGTT during pregnancy were significantly better than from fasting glucose and insulin values. However, separate prediction equations are necessary for pregnant women with NGT and women with GDM.
Insulin Resistance Syndrome Predicts Coronary Heart Disease Events in Elderly Type 2 Diabetic Men
Authors: Kuusisto Johanna , Lempiäinen Päivi , Mykkänen Leena , Laakso Markku
Published: March 2007

OBJECTIVE—To investigate whether cardiovascular risk factors cluster with hyperinsulinemia in elderly type 2 diabetic subjects and, if so, whether this clustering predicts coronary heart disease (CHD) events during a 7-year follow-up.

RESEARCH DESIGN AND METHODS—Clustering of cardiovascular risk factors was analyzed by factor analysis. Cox regression models were used to investigate whether these clusters (factors) predict CHD events (CHD death or nonfatal myocardial infarction) during a 7-year follow-up in 229 type 2 diabetic subjects aged 65–74 years.

RESULTS—There were 70 CHD events (21 in men and 49 in women) during the follow-up period. In diabetic men, components of the insulin resistance syndrome (IRS) loaded on Factor 1 (the insulin resistance factor), which reflected high fasting insulin, obesity (high BMI), central obesity (high waist-to-hip ratio), high total triglycerides, and a short duration of diabetes. Only this IRS factor predicted CHD events in multivariate Cox regression analysis (hazard ratio [HR] 1.71, 95% CI 1.08–2.71, P = 0.022). In diabetic women, components of IRS loaded on two factors, none of which predicted CHD events. In women, only Factor 4, characterized by advanced age, left ventricular hypertrophy on electrocardiogram, high alcohol consumption, high systolic blood pressure, and albuminuria, predicted CHD events in multivariate Cox regression analysis (1.34, 1.03–1.74, P = 0.03).

CONCLUSIONS—IRS is a risk factor for CHD in elderly type 2 diabetic men.
Admission Plasma Glucose
Authors: Zindrou Dlear , Taylor Kenneth M. , Bagger Jens Peder
Published: March 2007

OBJECTIVE—To investigate the relationship between admission plasma glucose and 30-day mortality after primary isolated coronary artery bypass grafting (CABG) in nondiabetic patients.

RESEARCH DESIGN AND METHODS—All nondiabetic patients with admission plasma glucose measurement undergoing primary isolated CABG from 1993 to 1997 were included in this study.

RESULTS—In 878 consecutive patients (155 women), overall mortality was 3.4% (95% CI 2.3–4.8). The mortality rate in women (n = 11; 7.1%, 3.6–12.3) was higher than in men (n = 19; 2.6%, 1.6–4.1) (P = 0.01). There was a positive correlation between plasma glucose and 30-day mortality among women only (P = 0.0001). There was a higher mortality rate in the upper two glucose quartiles (11.7%, 5.5–21.0) compared with the lower two quartiles (2.6%, 3.0–8.9) in the female patients (P = 0.03); a plasma glucose of 6.0 mmol/l separated high- and low-mortality groups. Furthermore, women in the upper two glucose quartiles had a fourfold higher mortality rate than men in the similar quartiles (P = 0.002). Among men, there was no difference in mortality rate across glucose quartiles. In a multivariate analysis, admission plasma glucose, history of thyroid disease, left ventricular ejection fraction <0.35, operation bypass time, and perioperative myocardial infarction were independently associated with mortality.

CONCLUSIONS—Women with admission plasma glucose ≤6.0 mmol/l and men across the whole range of glucose values had similar mortality rates after CABG. The surplus female mortality was found only in subjects with plasma glucose >6 mmol/l. Further studies are needed to appraise the possible influence of glucose status on outcome from CABG in nondiabetic subjects.
Evidence of Primary β-Cell Destruction by T-Cells and β-Cell Differentiation From Pancreatic Ductal Cells in Diabetes Associated With Active Autoimmune Chronic Pancreatitis
Authors: Tanaka Shoichiro , Kobayashi Tetsuro , Nakanishi Koji , Okubo Minoru , Murase Toshio , Hashimoto Masaji , Watanabe Goro , Matsushita Hiroshi , Endo Yuzo , Yoshizaki Hideo , Kosuge Tomoo , Sakamoto Michiie , Takeuchi Kazuo
Published: March 2007

OBJECTIVE—Diabetes associated with autoimmune chronic pancreatitis (ACP) is a subtype of diabetes that is responsive to corticosteroid treatment of progressive endocrine and exocrine dysfunction. However, little is known about pathological changes of islet and exocrine pancreas in ACP.

RESEARCH DESIGN AND METHODS—We examined pancreatic specimens obtained on biopsy from four diabetic men with ACP (mean [range]: age 62 years [48–78], duration of ACP 3 months [1–5], duration of diabetes 1 month [0–3]) morphologically, immunohistochemically, and morphometrically.

RESULTS—The pancreatic specimens in all cases exhibited inflammatory cell infiltration surrounding ductal cells and extensive fibrosis. Some islets were infiltrated with mononuclear cells with disrupted β-cells. The subsets of T-cells infiltrated to the islets were mainly CD8+. Islet β-cell volume was decreased; the mean percentage area of β-cells in the islets in four cases with ACP were 16% (range 13–20) (P = 0.0015 vs. type 2 diabetic patients, 48% [27–73], n = 8; P = 0.0002 vs. nondiabetic control subjects, 58% [39–77], n = 7). Preserved ductal cells were surrounded predominantly by CD8+ or CD4+ T-cells. Some cytokeratin 19–positive ductal cells contained insulin and glucagon, representing upregulated differentiation of islet cells from ductal cells. Insulin promoter factor-1 (IPF-1) was hyperexpressed in insulin-containing ductal cells.

CONCLUSIONS—Diabetes associated with ACP is caused by T-cell–mediated mechanisms primarily involving islet β-cells as well as pancreatic ductal cells. In ACP, ductal islet precursor cells were associated with IPF-1 hyperexpression, suggesting a critical role of IPF-1 on islet cell differentiation and eventual β-cell restoration.
Muscle Fiber Composition and Capillary Density in Turner Syndrome
Authors: Gravholt Claus Højbjerg , Nyholm Birgit , Saltin Bengt , Schmitz Ole , Christiansen Jens Sandahl
Published: March 2007

OBJECTIVE—To assess muscle fiber composition and capillary density in Turner syndrome, a condition linked with insulin resistance and increased frequency of type 2 diabetes, and link these findings with insulin sensitivity and physical fitness.

RESEARCH DESIGN AND METHODS—A total of 10 patients with Turner syndrome who were off hormone replacement therapy (aged 32.7 ± 8.9 years) and a control group of 14 normal women (aged 35.6 ± 9.3 years) were studied. None of the participants had diabetes or any family history of type 2 diabetes. An oral glucose tolerance test was performed, and insulin sensitivity was assessed by homeostasis model assessment (HOMA) and a composite whole-body insulin sensitivity index (ISIcomp). Physical fitness was assessed, and a muscle biopsy was obtained.

RESULTS—Women with Turner syndrome were insulin resistant, as seen by a lower ISIcomp (P = 0.003) and increased glucose (P < 0.0005) and insulin (P = 0.01) levels at 120 min. Impaired glucose tolerance was present in most Turner syndrome patients (6 of 10), but not in the control subjects. Women with Turner syndrome had an increased size of type IIa fibers (P = 0.01), whereas the size of their type I and IIa fibers were comparable with the control group. The groups did not differ in percentage of type I, Iia, or IIx fibers, and there was no difference in the capillary density. Significant correlations were found among ISIcomp, the HOMA index (RHOMA), and the mean area of type IIa fibers (ISIcomp: r = −0.632, P = 0.002; RHOMA: r = 0.570, P = 0.006). Furthermore, capillaries/type IIa fibers correlated significantly with ISIcomp (r = −0.618, P = 0.01). There were no significant correlations between Vo2max and muscle fiber composition.

CONCLUSIONS—Healthy women with Turner syndrome are characterized by impaired glucose tolerance, insulin resistance, low physical capacity, and enlarged type IIa muscle fibers, indicating diminished oxygen and substrate supply for metabolic processes. These findings could be indicative of a prediabetic state.
Productivity and Medical Costs of Diabetes in a Large Employer Population
Authors: Ramsey Scott , Summers Kent H. , Leong Stephanie A. , Birnbaum Howard G. , Kemner Jason E. , Greenberg Paul
Published: March 2007

OBJECTIVE—The purpose of this study was to assess the economic burden of diabetes from an employer’s perspective. We analyzed the costs of diabetes, using claims data for an employed population and the prevalence of selected comorbid conditions.

RESEARCH DESIGN AND METHODS—The data source is a claims database from a national Fortune 100 manufacturer. It includes medical, pharmacy, and disability claims for all beneficiaries (n >100,000). Both medical and work productivity costs of diabetes patients are compared by age with those of matched control subjects from the overall beneficiary population. Out-of-pocket and intangible costs are excluded.

RESULTS—In 1998, the employer’s mean annual per capita costs were higher for all diabetes beneficiaries than for control subjects ($7,778 ± 16,176 vs. $3,367 ± 8,783; P < 0.0001), yielding an incremental cost of $4,410 ± 18,407 associated with diabetes. The medical and productivity costs for employees with diabetes were significantly (P < 0.0008) higher than for control subjects. The incremental cost of diabetes among employees ranged from $4,671 (aged 18–35 years) to $4,369 (aged 56–64 years).

CONCLUSIONS—Diabetes imposes a significant economic burden on employers, particularly when including productivity costs. Employers should select health plans that provide enriched benefits to diabetes patients, including ready access to medical and pharmacy services as well as aggressive diabetes management programs.
Determinants of Mild Gestational Hyperglycemia and Gestational Diabetes Mellitus in a Large Dutch Multiethnic Cohort
Authors: Weijers Rob N.M. , Bekedam Dick J. , Smulders Yvo M.
Published: March 2007

OBJECTIVE—The purpose of this study was to identify independent determinants of mild gestational hyperglycemia (MGH) and gestational diabetes mellitus (GDM) and to assess the correlation between fasting glucose and C-peptide levels among control, MGH, and GDM women.

RESEARCH DESIGN AND METHODS—A total of 1,022 consecutive women were evaluated with a 1-h 50-g glucose challenge test (GCT) at between 16 and 33 weeks of gestation. Women with a capillary whole-blood glucose ≥7.8 mmol/l in the GCT underwent a 3-h 100-g oral glucose tolerance test (OGTT). On the basis of a positive GCT, the women with a positive OGTT were classified as GDM, whereas the women with a negative OGTT were classified as MGH. The following data were collected for all women: age, prepregnancy BMI, ethnicity, clinical and obstetric history, pregnancy outcome, and C-peptide level.

RESULTS—A total of 813 women (79.6%) were normal, 138 (13.5%) had MGH, and 71 (6.9%) had GDM. There was a stepwise significant increase in mean fasting glucose (3.6 ± 0.4, 3.9 ± 0.4, and 4.7 ± 0.7 mmol/l, respectively) and C-peptide level (0.60 [0.1–2.4], 0.86 [0.3–2.0], and 1.00 [0.5–1.6] nmol/l, respectively) among the three diagnostic groups. Maternal age, non-Caucasian ethnicity, and prepregnancy BMI were associated with GDM, whereas only maternal age and prepregnancy BMI were associated with MGH. A positive correlation between levels of fasting glucose and C-peptide was found in control women (r = 0.39 [95% CI 0.31–0.46]). A similar result was seen in MGH women (r = 0.38 [95% CI 0.23–0.52]), whereas the correlation between fasting glucose and C-peptide was nearly lost in GDM women (r = 0.14 [CI −0.09 to 0.36]). The fasting C-peptide–to–glucose ratio was reduced by 60% in GDM patients versus control subjects and MGH patients (0.41 ± 0.25 vs. 0.70 ± 0.20 and 0.73 ± 0.23, P < 0.001).

CONCLUSIONS—Of the well-known independent determinants of GDM, only maternal age and prepregnancy BMI were associated with MGH. It appears that additional factors promoting loss of β-cell function distinguish MGH from GDM. One of these factors appears to be ethnicity.
Older Women With Diabetes Have a Higher Risk of Falls
Authors: Schwartz Ann V. , Hillier Teresa A. , Sellmeyer Deborah E. , Resnick Helaine E. , Gregg Edward , Ensrud Kristine E. , Schreiner Pamela J. , Margolis Karen L. , Cauley Jane A. , Nevitt Michael C. , Black Dennis M. , Cummings Steven R. ,   For the Study of Osteoporotic Fractures Research Group
Published: March 2007

OBJECTIVE—To determine whether older women with diabetes have an increased risk of falls and whether known risk factors for falls account for any increased risk.

RESEARCH DESIGN AND METHODS—This prospective cohort study included 9,249 women ≥67 years of age enrolled in the Study of Osteoporotic Fractures. Diabetes was determined by questionnaire at baseline. Physical performance was measured at the second examination. Subsequently, falls were ascertained every 4 months by postcard.

RESULTS—A total of 629 (6.8%) women had diabetes, including 99 who used insulin. During an average of 7.2 years, 1,640 women (18%) fell more than once a year. Diabetes, stratified by insulin use, was associated with an increased risk of falling more than once a year (age-adjusted odds ratio [OR] 1.68 [95% CI 1.37–2.07] for non–insulin-treated diabetes; age-adjusted OR 2.78 [1.82–4.24] for insulin-treated diabetes). In the first 2 years of follow-up, women with diabetes were not more likely to fall than women without diabetes (44 vs. 42%; P = 0.26), but they had more falls (3.1 vs. 2.4; P < 0.01). Women with diabetes were more likely to have other risk factors for falls, which appeared to account for the increased risk of falls associated with non–insulin-treated diabetes (adjusted OR 1.18 [0.87–1.60]) but not insulin-treated diabetes (adjusted OR 2.76 [1.52–5.01]).

CONCLUSIONS—Older women with diabetes have an increased risk of falling, partly because of the increased rates of known fall risk factors, and may benefit from interventions to prevent falls. Further research is needed to determine whether diabetes treatment reduces fall risk.
Exercise Training Improves Vascular Endothelial Function in Patients with Type 1 Diabetes
Authors: Fuchsjäger-Mayrl Gabriele , Pleiner Johannes , Wiesinger Günther F. , Sieder Anna E. , Quittan Michael , Nuhr Martin J. , Francesconi Claudia , Seit Hans-Peter , Francesconi Mario , Schmetterer Leopold , Wolzt Michael
Published: March 2007

OBJECTIVE—Impaired endothelial function of resistance and conduit arteries can be detected in patients with type 1 diabetes. We studied whether a persistent improvement of endothelial function can be achieved by regular physical training.

RESEARCH DESIGN AND METHODS—The study included 26 patients with type 1 diabetes of 20 ± 10 years’ duration and no overt angiopathy; 18 patients (42 ± 10 years old) participated in a bicycle exercise training program, and 8 patients with type 1 diabetes (33 ± 11 years old) served as control subjects. Vascular function of conduit arteries was assessed by flow-mediated and endothelium-independent dilation of the brachial artery and of resistance vessels by the response of ocular fundus pulsation amplitudes to intravenous NG-monomethyl-l-arginine (l-NMMA) at baseline, after 2 and 4 months of training, and 8 months after cessation of regular exercise.

RESULTS—Training increased peak oxygen uptake (Vo2max) by 13% after 2 months and by 27% after 4 months (P = 0.04). Flow-mediated dilation (FMD) of the brachial artery increased from 6.5 ± 1.1 to 9.8 ± 1.1% (P = 0.04) by training. l-NMMA administration decreased fundus pulsation amplitude (FPA) by 9.1 ± 0.9% before training and by 13.4 ± 1.5% after 4 months of training (P = 0.02). Vo2max, FMD, and FPA were unchanged in the control group. Vascular effects from training were abrogated 8 months after cessation of exercise.

CONCLUSIONS—Our study demonstrates that aerobic exercise training can improve endothelial function in different vascular beds in patients with long-standing type 1 diabetes, who are at considerable risk for diabetic angiopathy. However, the beneficial effect on vascular function is not maintained in the absence of exercise.