bluuebunny/crossref_metadata_2025 huggingface dataset:
Randomized Cross-Over Trial of Insulin Glargine Plus Lispro or NPH Insulin Plus Regular Human Insulin in Adolescents With Type 1 Diabetes on Intensive Insulin Regimens
Authors: Murphy Nuala P. , Keane Suzanne M. , Ong Ken K. , Ford-Adams Martha , Edge Julie A. , Acerini Carlo L. , Dunger David B.
Published: March 2007

OBJECTIVE—To compare blood glucose control and incidence of nocturnal hypoglycemia in adolescents with type 1 diabetes on multiple injection regimens managed with either an insulin analog combination or NPH insulin plus regular human insulin.

RESEARCH DESIGN AND METHODS—In a randomized cross-over study, 28 adolescents with type 1 diabetes on multiple injection therapy received either insulin glargine prebedtime plus lispro preprandially (LIS/GLAR) or NPH insulin prebedtime plus regular human insulin preprandially (R/NPH). During each 16-week treatment arm, subjects completed home blood glucose profiles, and at the end of each treatment arm, they were admitted for an overnight metabolic profile. A total of 25 subjects completed the study.

RESULTS—Compared with R/NPH therapy, LIS/GLAR was associated with lower mean blood glucose levels (LIS/GLAR versus R/NPH): fasting (8.0 vs. 9.2 mmol/l, P < 0.0001), 2 h postbreakfast (8.1 vs. 10.7 mmol/l, P < 0.0005), prelunch (8.9 vs. 10.1 mmol/l, P < 0.01), and 2 h postlunch (8.0 vs. 9.5 mmol/l, P < 0.002). However, there was no difference in mean blood glucose levels before or after the evening meal. Incidence of nocturnal hypoglycemia on overnight profiles was 43% lower on LIS/GLAR compared with R/NPH therapy; however, there was no difference in rates of self-reported symptomatic hypoglycemia. Total insulin dose required to achieve target blood glucose control was lower on LIS/GLAR (1.16 IU/kg) compared with R/NPH therapy (1.26 IU/kg, P < 0.005), but there was no significant difference in HbA1c levels (LIS/GLAR versus R/NPH: 8.7 vs. 9.1%, P = 0.13).

CONCLUSIONS—Combination therapy with insulin glargine plus lispro reduced the incidence of nocturnal hypoglycemia and was at least as effective as R/NPH insulin therapy in maintaining glycemic control in adolescents on multiple injection regimens.
A Comparison of Diabetes Education Administered Through Telemedicine Versus in Person
Authors: Izquierdo Roberto E. , Knudson Paul E. , Meyer Suzanne , Kearns Joann , Ploutz-Snyder Robert , Weinstock Ruth S.
Published: March 2007

OBJECTIVE—To determine whether diabetes education can be provided as effectively through telemedicine technology as through in-person encounters with diabetes nurse and nutrition educators.

RESEARCH DESIGN AND METHODS—A total of 56 adults with diabetes were randomized to receive diabetes education in person (control group) or via telemedicine (telemedicine group) and were followed prospectively. The education consisted of three consultative visits with diabetes nurse and nutrition educators. The in-person and telemedicine groups were compared using measures of glycemic control (HbA1c) and questionnaires to assess patient satisfaction and psychosocial functioning as related to diabetes. Outcome measures were obtained at baseline, immediately after the completion of diabetes education, and 3 months after the third educational visit.

RESULTS—Patient satisfaction was high in the telemedicine group. Problem Areas in Diabetes scale scores improved significantly with diabetes education (adjusted P < 0.05, before vs. immediately after education and 3 months after education), and the attainment of behavior-change goals did not differ between groups. With diabetes education, HbA1c improved from 8.6 ± 1.8% at baseline to 7.8 ± 1.5% immediately after education and 7.8 ± 1.8% 3 months after the third educational visit (unadjusted P < 0.001, P = 0.089 adjusted for BMI and age), with similar changes observed in the telemedicine and in-person groups.

CONCLUSIONS—Diabetes education via telemedicine and in person was equally effective in improving glycemic control, and both methods were well accepted by patients. Reduced diabetes-related stress was observed in both groups. These data suggest that telemedicine can be successfully used to provide diabetes education to patients.
Menstrual Cycle Differences Between Women With Type 1 Diabetes and Women Without Diabetes
Authors: Strotmeyer Elsa S. , Steenkiste Ann R. , Foley Thomas P. , Berga Sarah L. , Dorman Janice S.
Published: March 2007

OBJECTIVE—To evaluate menstrual cycle histories among women with type 1 diabetes, their sisters, and unrelated control subjects without diabetes across all reproductive ages.

RESEARCH DESIGN AND METHODS—Menstrual and reproductive histories were obtained by questionnaire from 143 women with type 1 diabetes, 186 sisters without diabetes, and 158 unrelated control subjects without diabetes participating in the Familial Autoimmune and Diabetes study.

RESULTS—Women with type 1 diabetes had more menstrual problems (long cycles, long menstruation, and heavy menstruation) before age 30 years than sisters and control subjects. These differences were all statistically significant, except for heavy menstruation at age <20 years. No differences were observed after age 30 years. Women with type 1 diabetes experienced later menarche, earlier natural menopause, fewer pregnancies, and more stillbirths than women without diabetes. Multiple regression analyses revealed that type 1 diabetes caused an approximate twofold increased risk of any menstrual problem before age 30 years. These were primarily related to long cycles and long menstruation in women aged <20 and 20–29 years, as well as with heavy menstruation from 20 to 29 years. Oral contraceptives were protective for any menstrual problem and heavy menstruation from 30 to 39 years of age. With history of pregnancy from 20 to 40 years of age, any menstrual problem and long menstruation were more likely.

CONCLUSIONS—The results suggest that type 1 diabetes is an independent risk factor for menstrual disturbances in young adults. Future studies may determine whether addressing menstrual disturbances improves quality of life and health for these women.
Type 2 Diabetes in Asian-Indian Urban Children
Authors: Ramachandran Ambady , Snehalatha Chamukuttan , Satyavani Kumpatla , Sivasankari Selvaraj , Vijay Viswanathan
Published: March 2007

OBJECTIVE—Due to a background of high prevalence of type 2 diabetes and the increasing rate of obesity occurring in relatively young urban children, we felt the need to look for type 2 diabetes in children.

RESEARCH DESIGN AND METHODS—A study of cases of type 2 diabetes with age at diagnosis of ≤15 years seen at a diabetes speciality center in Chennai, India, is reported. A total of 18 children (5 boys and 13 girls) aged 9–15 years with insidious onset of diabetes responding to oral antidiabetic agents (ODAs) for periods from 2 months to 12 years were studied. Clinical details, anthropometry, and details of family history of diabetes were elicited. All of them were tested for the presence of anti-GAD65 antibodies and for pancreatic β-cell reserve by measuring serum C-peptide response (radioimmunoassay procedures).

RESULTS—All children showed a response to ODAs, had good β-cell reserve (≥0.6 pmol/ml on stimulation), and negligible GAD65 antibodies indicating the presence of type 2 diabetes. The children were nonketotic; nine were obese, four had acanthosis nigricans, and one had polycystic ovary syndrome. Positive family history of diabetes was present in all cases.

CONCLUSIONS—The clinical, immunological, and biochemical profile showed that the children had type 2 diabetes. The profile of type 2 diabetes was similar to that described in children in many other countries. Although less common than type 1 diabetes, type 2 diabetes in children is a condition that needs to be recognized and looked for in Asian-Indians.
Diabetes and Impaired Fasting Glycemia in a Rural Population of Bangladesh
Authors: Sayeed M. Abu , Mahtab Hajera , Khanam Parvin Akter , Latif Zafar Abdul , Ali S. M. Keramat , Banu Akhter , Ahren Bo , Azad Khan A.K.
Published: March 2007

OBJECTIVE—To determine the prevalence of type 2 diabetes and impaired fasting glycemia (IFG) in a rural population of Bangladesh.

RESEARCH DESIGN AND METHODS—A cluster sampling of 4,923 subjects ≥20 years old in a rural community were investigated. Fasting plasma glucose, blood pressure, height, weight, and girth of waist and hip were measured. BMI and waist-to-hip ratio (WHR) were calculated. Total cholesterol, triglycerides, and HDL cholesterol were also estimated. We used the 1997 American Diabetes Association diagnostic criteria.

RESULTS—The crude prevalence of type 2 diabetes was 4.3% and IFG was 12.4%. The age-standardized prevalence of type 2 diabetes (95% CI) was 3.8% (3.12–4.49) and IFG was 13.0% (11.76–14.16). The subjects with higher family income had significantly higher prevalence of type 2 diabetes (5.9 vs. 3.5%, P < 0.001) and IFG (15.6 vs. 10.8%, P < 0.001) than those with lower income. Employing logistic regression in different models, we found that wealthy class, family history of diabetes, reduced physical exercise, and increased age, BMI, and WHR were the important predictors of diabetes. Total cholesterol, triglycerides, and HDL cholesterol showed no association with diabetes and IFG.

CONCLUSIONS—The prevalence of diabetes and IFG in the rural population was found to be on the increase compared with the previous reports of Bangladesh and other Asian studies. Older age, higher obesity, higher income, family history of diabetes, and reduced physical activity were proved significant risk factors for diabetes and IFG, whereas plasma lipids showed no association with diabetes and IFG. Further study may address whether diabetes is causally associated with insulin deficiency or insulin resistance.
Absence of Adverse Effects of Severe Hypoglycemia on Cognitive Function in School-Aged Children With Diabetes Over 18 Months
Authors: Wysocki Tim , Harris Michael A. , Mauras Nelly , Fox Larry , Taylor Alexandra , Jackson S. Craig , White Neil H.
Published: March 2007

OBJECTIVE—Some children with type 1 diabetes may be at risk of cognitive impairments, but mechanisms of this effect have not been confirmed. The objective of this study was to determine whether severe hypoglycemia (SH) in children with type 1 diabetes is associated with cognitive decline over 18 months.

RESEARCH DESIGN AND METHODS—A sample of 142 6- to 15-year-old children with type 1 diabetes (mean age 11.6 ± 2.7 years) enrolled in a trial of intensive therapy (IT) or usual care (UC) were tested with the Das-Naglieri Cognitive Assessment System at baseline and after 9 and 18 months. Episodes of SH were recorded by parents and reported promptly for verification by study nurses. HbA1c was measured quarterly.

RESULTS—Over 18 months, 58 of 142 patients (41%) experienced 111 SH episodes, with a RR of SH of 1.12 for IT over UC. Neither occurrence nor frequency of SH was associated with decline in full-scale intelligence quotient (IQ), standard scores for planning, attention, simultaneous processing, or successive processing, or scaled scores on any of eight subtests. The same findings emerged when only patients who had experienced hypoglycemic seizures or coma were included in the SH group for analyses. These effects persisted when the child’s age, sex, type 1 diabetes duration, and age at diagnosis were controlled statistically. HbA1c during the trial was not associated with cognitive changes.

CONCLUSIONS—SH did not induce adverse changes in the measures of cognitive function administered to 6- to 15-year-old children with type 1 diabetes in this study. Although SH should be avoided in all children with diabetes, these episodes did not have adverse effects on cognition in this age-group over 18 months.
Accuracy of an Electrochemical Sensor for Measuring Capillary Blood Ketones by Fingerstick Samples During Metabolic Deterioration After Continuous Subcutaneous Insulin Infusion Interruption in Type 1 Diabetic Patients
Authors: Guerci Bruno , Benichou Muriel , Floriot Michèle , Bohme Philip , Fougnot Sebastien , Franck Patricia , Drouin Pierre
Published: March 2007

OBJECTIVE—This study was designed to test the accuracy of capillary ketonemia for diagnosis of ketosis after interruption of insulin infusion.

RESEARCH DESIGN AND METHODS—A total of 18 patients with type 1 diabetes treated by external pump were studied during pump stop for 5 h. Plasma and capillary ketonemia and ketonuria were determined every hour from 7:00 a.m. (time 0 min = T0) to 12:00 p.m. (time 300 min = T300). Plasma β-hydroxybutyrate (β-OHB) levels were measured by an enzymatic end point spectrophotometric method, and capillary β-OHB levels were measured by an electrochemical method (MediSense Optium meter). Ketonuria was measured by a semiquantitative test (Ketodiastix). Positive ketosis was defined by a value of ≥0.5 mmol/l for ketonemia and ≥4 mmol/l (moderate) for ketonuria.

RESULTS—After stopping the pump, concentrations of β-OHB in both plasma and capillary blood increased significantly at time 60 min (T60) compared with T0 (P < 0.001), reaching maximum levels at T300 (1.30 ± 0.49 and 1.23 ± 0.78 mmol/l, respectively). Plasma and capillary β-OHB values were highly correlated (r = 0.94, P < 0.0001). For diagnosis of ketosis, capillary ketonemia has a higher sensitivity and negative predictive value (80.4 and 82.5%, respectively) than ketonuria (63 and 71.8%, respectively). For plasma glucose levels ≥250 mg/dl, plasma and capillary ketonemia were found to be more frequently positive (85 and 78%, respectively) than ketonuria (59%) (P = 0.017). The time delay to diagnosis of ketosis was significantly higher for ketonuria than for plasma ketonemia (212 ± 67 vs. 140 ± 54 min, P = 0.0023), whereas no difference was noted between plasma and capillary ketonemia.

CONCLUSIONS—The frequency of screening for ketosis and the efficiency of detection of ketosis definitely may be improved by the use of capillary blood ketone determination in clinical practice.
The Continuous Glucose Monitoring System Is Useful for Detecting Unrecognized Hypoglycemias in Patients With Type 1 and Type 2 Diabetes but Is Not Better Than Frequent Capillary Glucose Measurements for Improving Metabolic Control
Authors: Chico Ana , Vidal-Ríos Pablo , Subirà Montserrat , Novials Anna
Published: March 2007

OBJECTIVE—To evaluate whether the continuous glucose monitoring system (CGMS; MiniMed, Sylmar, CA) is useful for investigating the incidence of unrecognized hypoglycemias in type 1 and type 2 diabetic patients and for improving metabolic control in type 1 diabetic patients.

RESEARCH DESIGN AND METHODS—A total of 70 diabetic subjects (40 type 1 and 30 type 2 subjects) were monitored using the CGMS. The number of unrecognized hypoglycemias was registered. Furthermore, the 40 type 1 diabetic patients whose treatment was modified in accordance with the information obtained from the CGMS were compared with a control group of 35 different type 1 diabetic patients using intensive capillary glucose measurements. HbA1c levels were measured before the monitoring period and 3 months later.

RESULTS—The CGMS detected unrecognized hypoglycemias in 62.5% of the type 1 diabetic patients and in 46.6% of the type 2 diabetic patients. We found that 73.7% of all events occurred at night. HbA1c concentrations decreased significantly in both the group of type 1 diabetic subjects monitored with the CGMS (from 8.3 ± 1.6 to 7.5 ± 1.2%, P < 0.01) and the control group (from 8.0 ± 1.4 to 7.5 ± 0.8%, P < 0.01). The greatest reduction was observed in the subgroup of patients who started continuous subcutaneous insulin infusion therapy, both in the CGMS-monitored and control groups (from 9.4 ± 2 to 7.2 ± 1.4% and from 8.1 ± 1.8 to 7.1 ± 0.6%, respectively).

CONCLUSIONS—The CGMS is useful for detecting unrecognized hypoglycemias in type 1 and type 2 diabetic subjects; however, it is not better than standard capillary glucose measurements for improving metabolic control of type 1 diabetic subjects, regardless of the therapeutic regimen.
Serum Extracellular Superoxide Dismutase in Patients With Type 2 Diabetes
Authors: Kimura Fumiaki , Hasegawa Goji , Obayashi Hiroshi , Adachi Tetsuo , Hara Hirokazu , Ohta Mitsuhiro , Fukui Michiaki , Kitagawa Yoshihiro , Park Hyohun , Nakamura Naoto , Nakano Koji , Yoshikawa Toshikazu
Published: March 2007

OBJECTIVE—The aim of this study was to determine the distribution of serum extracellular superoxide dismutase (EC-SOD) concentrations in patients with type 2 diabetes and to assess whether increased EC-SOD concentration is associated with the development of diabetic vascular complications.

RESEARCH DESIGN AND METHODs—Serum EC-SOD concentrations were determined in 222 patients with type 2 diabetes and 75 healthy control subjects by an enzyme-linked immunosorbent assay. All subjects had the EC-SOD domain genotyped.

RESULTS—The serum EC-SOD concentrations showed a distinct bimodal distribution in both patients with diabetes and control subjects. All subjects with the high-level phenotype carried the Arg213Gly mutation. The frequency of this variant was similar in the diabetes and control groups. Within the group of subjects with the common EC-SOD phenotype, the serum EC-SOD concentration (mean ± SE) was significantly higher in patients with type 2 diabetes (99.3 ± 1.3 ng/ml) compared with the control subjects (68.4 ± 2.3 ng/ml, P < 0.01). Stepwise multiple regression analysis of the data from the diabetic common phenotype group showed a significant relationship between serum EC-SOD concentration and duration of diabetes (F = 5.31), carotid artery intimal-media thickness (F = 8.24), and severity of nephropathy (F = 16.05) and retinopathy (F = 4.43).

CONCLUSIONS—We observed a strong relationship between the serum concentration of EC-SOD and the severity of both micro- and macrovascular diabetic complications. These findings suggest that serum EC-SOD concentration levels may be a marker of vascular injury, possibly reflecting hyperglycemia-induced oxidative injury to the vascular endothelium and decreased binding of EC-SOD to the vascular wall.
Decreasing Incidence of Severe Diabetic Microangiopathy in Type 1 Diabetes
Authors: Hovind Peter , Tarnow Lise , Rossing Kasper , Rossing Peter , Eising Stefanie , Larsen Nicolai , Binder Christian , Parving Hans-Henrik
Published: March 2007

OBJECTIVE—Conflicting evidence of a decline in incidence of microvascular complications in type 1 diabetes during the last decades has been reported. To assess recent trends in the cumulative incidence of diabetic microangiopathy in type 1 diabetes, we analyzed data from long-term prospective observational studies lasting ≥20 years.

RESEARCH DESIGN AND METHODS—A total of 600 Caucasian patients with onset of type 1 diabetes between 1965 and 1984 were followed until death or until the year 2000. Patients were divided into four groups based on the year of diabetes onset: group A, 1965–1969 (n = 113); group B, 1970–1974 (n = 130); group C, 1975–1979 (n = 113); and group D, 1979–1984 (n = 244). Group A, B, and C are prevalence cohorts identified in 1984; group D is an inception cohort.

RESULTS—In patients followed for ≥20 years, the cumulative incidence (95% CI) of diabetic nephropathy after 20 years of diabetes (urinary albumin excretion >300 mg/24 h) was reduced in patients with more recent diabetes onset (groups A–D): 31.1% (22.5–39.7) vs. 28.4% (19.8–37.0) vs. 18.9% (10.9–26.9) vs. 13.7% (6.2–21.2) (P = 0.015). Similarly, the cumulative incidence of proliferative retinopathy was as follows: 31.2% (22.2–39.8) vs. 30.3% (22.2–38.4) vs. 19.3% (11.2–27.4) vs. 12.5% (5.2–19.8) (P < 0.01). In the latter groups, antihypertensive treatment was started earlier, blood pressure and HbA1c were lower, and fewer patients smoked.

CONCLUSIONS—Our study demonstrates a decrease in the cumulative incidence of diabetic microangiopathy in type 1 diabetes over the past 35 years. Improved glycemic control, lower blood pressure (in part due to early aggressive antihypertensive treatment), and reduced prevalence of smoking rates were associated with the improved prognosis.
Trends in Lipid Management Among Patients With Coronary Artery Disease
Authors: Massing Mark W. , Foley Kathleen A. , Sueta Carla A. , Chowdhury Mridul , Biggs David P. , Alexander Charles M. , Simpson Ross J.
Published: March 2007

OBJECTIVE—To examine lipid management trends for coronary artery disease (CAD) patients with and without diabetes in order to determine whether those with diabetes are beginning to receive aggressive lipid management consistent with their elevated risk.

RESEARCH DESIGN AND METHODS—We used outpatient medical record data from 47,813 CAD patients seen at 295 medical practices participating in the Quality Assurance Program II between 1996 and 1998. Lipid testing rates, lipid treatment rates, and serum lipid concentrations are described for CAD patients with and without diabetes within strata of office visit date.

RESULTS—Lipid testing and treatment rates increased and mean lipid levels decreased markedly over time. Those with diabetes were 26% less likely to have a lipid profile and 17% less likely to receive a lipid-lowering medication than their nondiabetic counterparts, and this disparity did not diminish over time. Among treated patients, mean non-HDL cholesterol (non-HDL-C) and LDL cholesterol (LDL-C) declined less rapidly over time for patients with than without diabetes.

CONCLUSIONS—Although impressive progress was made in the outpatient lipid management of CAD patients, lipid management for CAD patients with diabetes improved no more rapidly, and in some cases less rapidly, than for nondiabetic patients. Given their higher risk, more effort is needed to ensure that CAD patients with diabetes receive aggressive lipid management.
Preventable Hospitalization Among Elderly Medicare Beneficiaries With Type 2 Diabetes
Authors: Niefeld Marlene R. , Braunstein Joel B. , Wu Albert W. , Saudek Christopher D. , Weller Wendy E. , Anderson Gerard F.
Published: March 2007

OBJECTIVE—To examine the impact of comorbid conditions on preventable hospitalizations among Medicare beneficiaries aged ≥65 years with type 2 diabetes.

RESEARCH DESIGN AND METHODS—Data were drawn from the 1999 Medicare Standard Analytic Files, a 5% nationally representative random sample of Medicare beneficiaries. The analysis sample included 193,556 Medicare beneficiaries aged ≥65 years with type 2 diabetes (ICD-9-CM codes 250.xx) who were enrolled in fee-for-service Medicare. Preventable hospitalization was assessed by measuring ambulatory care-sensitive conditions, an accepted measure of hospitalizations that could have been prevented with appropriate outpatient care. Multivariable analyses controlled for demographics; mortality; renal, ophthalmic, or neurological manifestations of diabetes; type of physician providing the outpatient care; and per capita community-level indicators of income and hospital beds.

RESULTS—Ninety-six percent of beneficiaries in the sample had a comorbidity, and 46% had five or more comorbidities. Among beneficiaries with type 2 diabetes, cardiovascular-related comorbidities were common and accounted for increased odds of preventable hospitalization, controlling for other factors. The likelihood of a preventable hospitalization increased in the presence of a claim for comorbid congestive heart failure, cardiomyopathy, coronary atherosclerosis, hypertension, or cardiac dysrythmias. Noncardiovascular comorbidities associated with a greater likelihood of preventable hospitalization included chronic obstructive pulmonary disease, asthma and lower respiratory disorders, Alzheimer’s disease/dementia, personality/anxiety disorders, depression, and osteoporosis. Our data suggest that nearly 7% of all hospitalizations could be avoided.

CONCLUSIONS—These findings support the need for improved outpatient care strategies to reduce the impact of comorbidity on unnecessary hospitalization in patients aged ≥65 years with type 2 diabetes.
Cutoff Values for Normal Anthropometric Variables in Asian Indian Adults
Authors: Snehalatha Chamukuttan , Viswanathan Vijay , Ramachandran Ambady
Published: March 2007

OBJECTIVE—Asian Indians have a high risk of developing glucose intolerance with small increments in their BMI. They generally have high upper-body adiposity, despite having a lean BMI. Therefore, this analysis was performed to find out the normal cutoff values for BMI and upper-body adiposity (waist circumference [WC] or waist-to-hip ratio [WHR]) by computing their risk associations with diabetes.

RESEARCH DESIGN AND METHODS—The risk of diabetes with stratified BMI, WC, or WHR was computed in 10,025 adults aged ≥20 years without a history of diabetes, and they were tested by oral glucose tolerance tests, using World Health Organization criteria. The calculations were performed separately in men and women using diabetes as the dependent variable versus normoglycemia (normal glucose tolerance) in multiple logistic regression analyses. Age-adjusted and stratified BMI, WC, or WHR were used as the independent variables, using the first stratum as the reference category. The upper limit of the stratum above which the risk association became statistically significant (P < 0.05) was considered to be the cutoff for normal values.

RESULTS—Normal cutoff values for BMI was 23 kg/m2 for both sexes. Cutoff values for WC were 85 and 80 cm for men and women, respectively; the corresponding WHRs were 0.88 and 0.81, respectively. Optimum sensitivity and specificity obtained from the receiver operator characteristic curve corresponded to these cutoff values.

CONCLUSIONS—The cutoff value for normal BMI for men and women was 23 kg/m2. The cutoff values for WC and WHR were lower in women than in men. The values were significantly lower compared with the corresponding values in white populations.
Importance of Obtaining Independent Measures of Insulin Secretion and Insulin Sensitivity During the Same Test
Authors: Tripathy Devjit , Wessman Ylva , Gullström Monica , Tuomi Tiinamaija , Groop Leif
Published: March 2007

OBJECTIVE—To validate and apply a method for independent assessment of insulin secretion and insulin sensitivity (SI) during the same test; that is, an intravenous glucose tolerance test followed by a euglycemic-hyperinsulinemic clamp, also called the Botnia clamp. This test was then applied to nondiabetic subjects with (FH+) and without (FH−) a first-degree family history of diabetes.

RESEARCH DESIGN AND METHODS—The Botnia clamp measures the first-phase insulin response (FPIR) to 0.3g/kg glucose i.v. and insulin sensitivity (M-value) from a 2-h euglycemic clamp begun 60 min after the glucose bolus. The M-value obtained during the Botnia clamp was compared with M-values obtained during a regular euglycemic clamp without prior glucose bolus. Repeated tests were performed in random order in subjects with normal and abnormal glucose tolerance. Finally, the test was applied to subjects with and without a family history of type 2 diabetes.

RESULTS—SI and insulin secretion from this test showed a high degree of reproducibility, and the M-value obtained with the Botnia clamp correlated strongly with the M-value from a euglycemic clamp without prior glucose bolus (r = 0.953, P < 0.005). FH+ subjects showed decreased SI (P = 0.02), but similar FPIR, compared with FH− subjects. However, insulin secretion adjusted for the degree of insulin resistance was significantly impaired (P = 0.04).

CONCLUSIONS—In conclusion, the Botnia clamp provides reliable and independent measures of SI and β-cell function during the same test. As illustrated above, knowledge of the degree of SI is mandatory when presenting data on insulin secretion.
Differences in LDL Oxidizability by Glycemic Status
Authors: Schwenke Dawn C. , D’Agostino Ralph B. , Goff David. C. , Karter Andrew J. , Rewers Marian J. , Wagenknecht Lynne E.
Published: March 2007

OBJECTIVE—To investigate differences in LDL oxidizability by glycemic status within the Insulin Resistance Atherosclerosis Study cohort.

RESEARCH DESIGN AND METHODS—LDL oxidizability (lag time and oxidation rate) after exposure to copper was compared among 352 subjects with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), newly diagnosed type 2 diabetes, and known type 2 diabetes.

RESULTS—After adjustment for age, clinic, ethnicity, sex, and smoking status, LDL oxidation rates differed by glycemic status (P = 0.001), with a strong trend (P = 0.0001) for reduced LDL oxidation rate with increasing extent and duration of glucose intolerance (2,378 ± 54, 2,208 ± 65, 2,145 ± 71, and 2,115 ± 48 arbitrary units [mean ± SE] for NGT, IGT, newly diagnosed type 2 diabetes, and known type 2 diabetes, respectively). Differences in LDL oxidation rate among groups were relatively unaltered by adjustment for lipids and lipoproteins, hypertension, BMI, and waist-to-hip ratio (WHR) and remained significant even after further adjustment for dietary antioxidants and fatty acids, as well as medications. LDL lag times differed marginally by glycemic status (P = 0.058), with similar values for NGT, IGT, and newly diagnosed type 2 diabetes (57–60 min) but higher values for known type 2 diabetes (65 ± 2). These differences were eliminated by further adjustment for lipids and lipoproteins, hypertension, BMI, and WHR.

CONCLUSIONS—We found that glycemic status influenced LDL oxidizability, with a paradoxical reduction in LDL oxidizability, as indicated by a lower LDL oxidation rate with increased extent and duration of glucose intolerance. This difference was only slightly attenuated by adjustment for relevant demographic, metabolic, dietary, and pharmacological factors that potentially influence LDL oxidation.
Effect of Acute Psychotic Stress in Nondiabetic Subjects on β-Cell Function and Insulin Sensitivity
Authors: Shiloah Eli , Witz Shula , Abramovitch Yehuda , Cohen Ohad , Buchs Andreas , Ramot Yoram , Weiss Mordechai , Unger Abraham , Rapoport Micha J.
Published: March 2007

OBJECTIVE—To determine the effect of acute psychotic stress on glucose homeostasis in nondiabetic subjects.

RESEARCH DESIGN AND METHODS—β-Cell function and insulin sensitivity were determined by the homeostasis model assessment in 39 nondiabetic patients with acute psychotic stress reaction admitted to a psychiatric ward. The clinical global impression (CGI) score was used to evaluate the level of psychological stress. Patients were assessed on admission, after 2 weeks, before discharge, and 6 months after discharge.

RESULTS—The mean CGI score decreased significantly with time: 5.3 ± 0.8 and 1.6 ± 0.7 on admission and predischarge, respectively (P < 0.001). This was associated with a significant reciprocal increase of mean β-cell function from 96.8 ± 33.2 to 134.4 ± 60% at admission and postdischarge, respectively (P < 0.003), and a decrease of mean insulin sensitivity from 101.7 ± 36 to 77.1 ± 34.8% (P < 0.001). In contrast, mean glucose and HbA1c levels did not change significantly. Subgroup analysis demonstrated that patients with the highest stress score on admission (≥6) had significantly higher glucose (P = 0.01) and insulin levels (P = 0.04) than patients with lower score (<6). Furthermore, insulin sensitivity and CGI score on admission were inversely correlated (r = −0.38, P < 0.02). In these patients, no correlation was found between β-cell function or insulin sensitivity and BMI.

CONCLUSIONS—These data indicate that β-cell function and insulin sensitivity are inversely correlated with acute psychotic stress.
Intensive Replacement of Basal Insulin in Patients With Type 1 Diabetes Given Rapid-Acting Insulin Analog at Mealtime
Authors: Rossetti Paolo , Pampanelli Simone , Fanelli Carmine , Porcellati Francesca , Costa Emanuela , Torlone Elisabetta , Scionti Luciano , Bolli Geremia B.
Published: March 2007

OBJECTIVE—To establish differences in blood glucose between different regimens of optimized basal insulin substitution in type 1 diabetic patients given lispro insulin at meals, i.e., NPH injected four times a day versus glargine insulin once daily at dinner or at bedtime.

RESEARCH DESIGN AND METHODS—A total of 51 patients with type 1 diabetes on intensive therapy (NPH four times/day and lispro insulin at each meal) were randomized to three different regimens of basal insulin substitution while continuing lispro insulin at meals: continuation of NPH four times/day (n = 17), once daily glargine at dinnertime (n = 17), and once daily glargine at bedtime (n = 17) for 3 months. Blood glucose targets were fasting, preprandial, and bedtime concentrations at 6.4–7.2 mmol/l and 2 h after meals at 8.0–9.2 mmol/l. The primary end point was HbA1c.

RESULTS—Mean daily blood glucose was lower with dinnertime glargine (7.5 ± 0.2 mmol/l) or bedtime glargine (7.4 ± 0.2 mmol/l) versus NPH (8.3 ± 0.2 mmol/l) (P < 0.05). A greater percentage of blood glucose values were at the target value with glargine at dinner and bedtime versus those with NPH (P < 0.05). HbA1c at 3 months did not change with NPH but decreased with glargine at dinnertime (from 6.8 ± 0.2 to 6.4 ± 0.1%) and glargine at bedtime (from 7.0 ± 0.2 to 6.6 ± 0.1%) (P < 0.04 vs. NPH). Total daily insulin doses were similar with the three treatments, but with glargine there was an increase in basal and a decrease in mealtime insulin requirements (P < 0.05). Frequency of mild hypoglycemia (self-assisted episodes, blood glucose ≤4.0 mmol/l) was lower with glargine (dinnertime 8.1 ± 0.8 mmol/l, bedtime 7.7 ± 0.9 mmol/l) than with NPH (12.2 ± 1.3 mmol/l) (episodes/patient-month, P < 0.04). In-hospital profiles confirmed outpatient blood glucose data and indicated more steady plasma insulin concentrations at night and before meals with glargine versus NPH (P < 0.05). There were no differences between glargine given at dinnertime and at bedtime.

CONCLUSIONS—Regimens of basal insulin with either NPH four times/day or glargine once/day in type 1 diabetic patients both result in good glycemic control. However, the simpler glargine regimen decreases the HbA1c level and frequency of hypoglycemia versus NPH. In contrast to NPH, which should be given at bedtime, insulin glargine can be administered at dinnertime without deteriorating blood glucose control.
Cell Surface Expression of LDL Receptor Is Decreased in Type 2 Diabetic Patients and Is Normalized by Insulin Therapy
Authors: Duvillard Laurence , Florentin Emmanuel , Lizard Gérard , Petit Jean-Michel , Galland Françoise , Monier Serge , Gambert Philippe , Vergès Bruno
Published: March 2007

OBJECTIVE—In type 2 diabetic patients with poor metabolic control, kinetic studies have demonstrated that LDL fractional catabolic rate (FCR) is slowed down, whereas it is normalized on insulin therapy. This study was designed to analyze whether variations in the expression of LDL receptors at the cell surface could explain the results observed in kinetic studies.

RESEARCH DESIGN AND METHODS—LDL receptors were quantified at the surface of mononuclear cells in fresh fasting blood samples by a flow cytometry method in 21 control subjects and 21 type 2 diabetic patients before and 3 months after the introduction of insulin therapy and concomitant removal of oral antidiabetic drugs.

RESULTS—Before insulin treatment, monocyte LDL receptor expression was reduced by 41% (6,439 ± 2,310 vs. 10,846 ± 2,764 receptors per monocyte, P < 0.001) in type 2 diabetic patients compared with control subjects. It increased by 57% after 3 months of insulin therapy (10,096 ± 5,657 vs. 6,439 ± 2,310, P < 0.01) and was similar to that observed in control subjects.

CONCLUSIONS—Our results suggest that insulin plays an important role in the in vivo expression of LDL receptors. Moreover, modulations in the expression of LDL receptors in type 2 diabetic patients either with poor metabolic control or on insulin therapy are likely to contribute to the variations of LDL FCR demonstrated by kinetic studies under those circumstances.
Patients on Atypical Antipsychotic Drugs
Authors: Lean Michael E.J. , Pajonk Frank-Gerald
Published: March 2007

Patients with schizophrenia are more likely than the general population to develop diabetes, which contributes to a high risk of cardiovascular complications; individuals with schizophrenia are two to three times more likely to die from cardiovascular disease than the general population. The risk of diabetes, and hence cardiovascular disease, is particularly increased by some of the new atypical antipsychotic drugs. Individuals taking an atypical antipsychotic drug, particularly younger patients under 40 years of age (odds ratio 1.63, 95% CI 1.23–2.16), represent an underrecognized group at high risk of type 2 diabetes. The mechanisms responsible for antipsychotic-induced diabetes remain unclear. Hypotheses include these drugs’ potential to cause weight gain, possibly through antagonism at the H1, 5-HT2A, or 5-HT2C receptors. Other mechanisms independent of weight gain lead to elevation of serum leptin and insulin resistance. Patients with psychoses have difficulties with diet and lifestyle interventions for diabetes and weight management. If hyperglycemia develops, withdrawal from antipsychotic medication will often be inappropriate, and a change to an atypical antipsychotic drug with lower diabetogenic potential should be considered, especially in younger patients. Management of psychoses should routinely include body weight and blood glucose monitoring and steps to promote exercise and minimize weight gain. Careful collaboration between the psychiatric and diabetology teams is essential to minimize the risk of diabetes in patients taking atypical antipsychotic medication and for effective management when it develops. This collaboration will also help minimize the already high risk of cardiovascular disease in individuals with schizophrenia.
Lowering of LDL Cholesterol Rather Than Moderate Weight Loss Improves Endothelium-Dependent Vasodilatation in Obese Women With Previous Gestational Diabetes
Authors: Bergholm Robert , Tiikkainen Mirja , Vehkavaara Satu , Tamminen Marjo , Teramo Kari , Rissanen Aila , Yki-Järvinen Hannele
Published: March 2007

OBJECTIVE—Effects of weight loss on vascular function are unknown. We compared, in the face of similar weight loss over 3–6 months, effects of orlistat (120 mg t.i.d., n = 23) and placebo (n = 24) on in vivo endothelial function in a high-risk group of obese (BMI 32.1 ± 0.4 kg/m2) premenopausal nondiabetic women with a history of gestational diabetes.

RESEARCH DESIGN AND METHODS—Forearm blood flow responses to intra-arterial infusions of acetylcholine (ACh) and sodium nitroprusside (SNP), body composition, and serum lipids were determined before and after weight loss.

RESULTS—Weight loss averaged 7.3 ± 0.2 kg (8.3 ± 0.1%) and 7.4 ± 0.2 kg (8.2 ± 0.1%) of initial body weight in the orlistat and placebo groups, respectively. Forearm and body compositions changed similarly in both groups. Responses to ACh increased by 41% to the low dose (5.9 ± 0.6 vs. 8.3 ± 0.3 for flow in the experimental/control arm, P < 0.01) and by 33% to the high dose (7.6 ± 0.8 vs. 10.1 ± 0.6, P < 0.001) in the orlistat group, but they remained unchanged in the placebo group. The blood flow responses to SNP did not differ significantly between the groups. LDL cholesterol decreased significantly in the orlistat group from 3.5 ± 0.2 to 3.0 ± 0.1 mmol/l (P < 0.01) but remained unchanged in the placebo group. Within the orlistat group, the decrease in LDL cholesterol correlated significantly with the improvement in the blood flow response to ACh (r = −0.44, P < 0.05).

CONCLUSIONS—Orlistat but not moderate (8%) weight loss per se improves endothelial function in women with previous gestational diabetes. This improvement is associated with a lowering of LDL cholesterol by orlistat.
Addition of Nateglinide to Rosiglitazone Monotherapy Suppresses Mealtime Hyperglycemia and Improves Overall Glycemic Control
Authors: Fonseca Vivian , Grunberger George , Gupta Shamita , Shen Sharon , Foley James E.
Published: March 2007

OBJECTIVE—To determine the effects of nateglinide added to rosiglitazone monotherapy on glycemic control and on postprandial glucose and insulin levels in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS—This 24-week, multicenter, double-blind, randomized study compared the efficacy of nateglinide (120 mg a.c.) and placebo added to rosiglitazone monotherapy (8 mg q.d.) in 402 patients with type 2 diabetes with HbA1c between 7 and 11% (inclusive). Efficacy parameters tested included HbA1c and plasma glucose and insulin levels in the fasting state and after a standardized meal challenge. Safety data were also collected.

RESULTS—In placebo-treated patients, HbA1c did not change (Δ = 0.0 ± 0.1%). In patients randomized to nateglinide, HbA1c decreased from 8.3 to 7.5% (Δ = −0.8 ± 0.1%, P < 0.0001 vs. placebo). Target HbA1c (<7.0%) was achieved by 38% of patients treated with combination therapy and by 9% of patients remaining on rosiglitazone monotherapy. In nateglinide-treated patients, fasting plasma glucose levels decreased by 0.7 mmol/l, 2-h postprandial glucose levels decreased by 2.7 mmol/l, and 30-min insulin levels increased by 165 pmol/l compared with no changes from baseline of these parameters with placebo added to rosiglitazone (P < 0.001).

CONCLUSIONS—By selectively augmenting early insulin release and decreasing prandial glucose excursions, nateglinide produced a clinically meaningful improvement in overall glycemic exposure in patients with type 2 diabetes inadequately controlled with rosiglitazone. Therefore, nateglinide substantially improves the likelihood of achieving a therapeutic target of HbA1c <7.0%.
The Efficacy and Safety of Dermagraft in Improving the Healing of Chronic Diabetic Foot Ulcers
Authors: Marston William A. , Hanft Jason , Norwood Paul , Pollak Richard ,   for the Dermagraft Diabetic Foot Ulcer Study Group
Published: March 2007

OBJECTIVE—To determine if a human fibroblast–derived dermal substitute could promote the healing of diabetic foot ulcers.

RESEARCH DESIGN AND METHODS—A randomized, controlled, multicenter study was undertaken at 35 centers throughout the U.S. and enrolled 314 patients to evaluate complete wound closure by 12 weeks. Patients were randomized to either the Dermagraft treatment group or control (conventional therapy). Except for the application of Dermagraft, treatment of study ulcers was identical for patients in both groups. All patients received pressure-reducing footwear and were allowed to be ambulatory during the study.

RESULTS—The results demonstrated that patients with chronic diabetic foot ulcers of >6 weeks duration experienced a significant clinical benefit when treated with Dermagraft versus patients treated with conventional therapy alone. With regard to complete wound closure by week 12, 30.0% (39 of 130) of Dermagraft patients healed compared with 18.3% (21 of 115) of control patients (P = 0.023). The overall incidence of adverse events was similar for both the Dermagraft and control groups, but the Dermagraft group experienced significantly fewer ulcer-related adverse events.

CONCLUSIONS—The data from this study show that Dermagraft is a safe and effective treatment for chronic diabetic foot ulcers.
Inflammatory Markers, Adiponectin, and Risk of Type 2 Diabetes in the Pima Indian
Authors: Krakoff Jonathan , Funahashi Tohru , Stehouwer Coen D.A. , Schalkwijk Casper G. , Tanaka Sachiyo , Matsuzawa Yuji , Kobes Sayuko , Tataranni P. Antonio , Hanson Robert L. , Knowler William C. , Lindsay Robert S.
Published: March 2007

OBJECTIVE—To examine the association between adiponectin, a known predictor of diabetes in Pima Indians, and markers of inflammation and endothelial function in nondiabetic subjects and to assess whether these markers predict later diabetes in a case-control study within a longitudinal health study in Pima Indians.

RESEARCH DESIGN AND METHODS—Participants with normal glucose tolerance at baseline were selected. Case subjects (who later developed type 2 diabetes), and control subjects (n = 71 pairs) were matched for BMI, age, and sex. Adiponectin, C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor-α, phospholipase A2 (sPLA2), soluble E-selectin (SE-selectin), soluble intracellular adhesion molecule-1, soluble vascular adhesion molecule-1, and von Willebrand factor (vWF) were measured in baseline samples.

RESULTS—Adiponectin was negatively correlated with CRP (r = −0.25, P < 0.05), IL-6 (r = −0.20, P < 0.05), sPLA2 (r = −0.22, P < 0.05), and SE-selectin (r = −0.20, P < 0.05). CRP and IL-6 did not predict diabetes. Only vWF predicted the development of diabetes (incidence rate ratio 0.67 for a 1-SD difference, 95% CI 0.41–1.00, P = 0.05), but this was not significant after adjustment for age, glucose, HbA1c, waist circumference, and fasting insulin (hazard rate ratio 0.73, 95% CI 0.46–1.16, P = 0.18).

CONCLUSIONS—Adiponectin is negatively correlated with markers of inflammation in vivo. In case and control subjects matched for BMI, with the exception of vWF, none of the inflammatory markers predicted diabetes. Adiponectin may be the link between adiposity, inflammation, and type 2 diabetes.
Intensified Blood Glucose Monitoring Improves Glycemic Control in Stable, Insulin-Treated Veterans With Type 2 Diabetes
Authors: Murata Glen H. , Shah Jayendra H. , Hoffman Richard M. , Wendel Christopher S. , Adam Karen D. , Solvas Patricia A. , Bokhari Syed U. , Duckworth William C.
Published: March 2007

OBJECTIVE—To examine the effect of intensified self-monitored blood glucose (SMBG) testing on glycemic control.

RESEARCH DESIGN AND METHODS—Subjects with stable, insulin-treated type 2 diabetes performed SMBG using an electronic blood glucose meter before all meals and at bedtime for 8 weeks. Baseline data were collected on demographics, clinical characteristics, diet, and exercise. HbA1c was measured at baseline, at 4 weeks, and at 8 weeks. After the intensified monitoring period, subjects resumed their usual monitoring. HbA1c was then measured at 24, 37, and 52 weeks. Multivariate linear regression was used to determine the effect of monitoring on glycemic control.

RESULTS—A total of 201 subjects completed the monitoring period. The baseline HbA1c (8.10 ± 1.67%) decreased during the monitoring period by 0.30 ± 0.68% (P < 0.001) at 4 weeks and by 0.36 ± 0.88% (P < 0.001) at 8 weeks. Although entry HbA1c and compliance independently predicted the week 8 HbA1c (r = 0.862, P < 0.001), standardized regression analysis found that compliance with the SMBG protocol influenced the week 8 HbA1c more than age, sex, BMI, exercise level, carbohydrate consumption, or treatment intensity at baseline. However, SMBG benefited only subjects whose testing compliance exceeded 75% or with an entry HbA1c >8.0%. Decreases in HbA1c (−0.31 ± 1.17%, P = 0.001) persisted in the 159 subjects followed for 52 weeks.

CONCLUSIONS—Intensified blood glucose monitoring improved glycemic control in a large cohort of stable, insulin-treated veterans with type 2 diabetes. SMBG provided a strong stimulus for improved self-care resulting in clinically important and sustained reductions in HbA1c.