bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Intensive Lifestyle and Metformin Therapy on Cardiovascular Disease Risk Factors in the Diabetes Prevention Program
Authors:   The Diabetes Prevention Program Research Group
Published: March 2007

OBJECTIVE—The Diabetes Prevention Program demonstrated the ability to delay or prevent type 2 diabetes in participants with impaired glucose tolerance (IGT). Participants with IGT are at high risk for cardiovascular disease (CVD), with a marked increase in the number and severity of CVD risk factors. We prospectively assessed the impact of our interventions on hypertension, dyslipidemia, and CVD events.
RESEARCH DESIGN AND METHODS—The study group consisted of 3,234 individuals with IGT randomly assigned to receive intensive lifestyle intervention, metformin, or placebo. Annual assessment of blood pressure, lipids, electrocardiogram, and CVD events was undertaken.
RESULTS—Hypertension was present in 30% of participants at study entry and then increased in the placebo and metformin groups, although it significantly decreased with intensive lifestyle intervention. Triglyceride levels fell in all treatment groups, but fell significantly more with intensive lifestyle intervention. Total cholesterol and LDL cholesterol levels were similar among treatment groups. Intensive lifestyle intervention significantly increased the HDL cholesterol level and reduced the cumulative incidence of the proatherogenic LDL phenotype B. At 3 years of follow-up, the use for pharmacologic therapy to achieve established goals in the intensive lifestyle group was 27–28% less for hypertension and 25% less for hyperlipidemia compared with placebo and metformin groups. Over an average of 3 years, 89 CVD events from 64 participants were positively adjudicated studywide, with no differences among treatment groups.
CONCLUSIONS—Lifestyle intervention improves CVD risk factor status compared with placebo and metformin therapy. Although no differences in CVD events were noted after 3 years, achieved risk factor modifications suggest that longer intervention may reduce CVD event rates.
Predictors of Changes in Glucose Tolerance Status in Obese Youth
Authors: Weiss Ram , Taksali Sara E. , Tamborlane William V. , Burgert Tania S. , Savoye Mary , Caprio Sonia 
Published: March 2007

OBJECTIVE—Type 2 diabetes in obese youth is an emerging problem. The metabolic and anthropometric predictors of change in glucose tolerance status in obese youth are unknown.
RESEARCH DESIGN AND METHODS—A total of 117 obese children and adolescents were studied by performing an oral glucose tolerance test (OGTT) at baseline and after ∼2 years. Data from both OGTTs and changes in weight were examined to identify youth at highest risk for developing diabetes and the factors that have the strongest impact on glucose tolerance.
RESULTS—Eighty-four subjects had normal glucose tolerance (NGT) and 33 impaired glucose tolerance (IGT) at baseline. Eight subjects (all of whom had IGT at baseline) developed type 2 diabetes, whereas 15 subjects with IGT reverted to NGT. In this cohort, severe obesity, impaired glucose tolerance, and African-American background emerged as the best predictors of developing type 2 diabetes, whereas fasting glucose, insulin, and C-peptide were nonpredictive. Changes in insulin sensitivity, strongly related to weight change, had a significant impact on the 2-h glucose level on the follow-up study.
CONCLUSIONS—Severely obese children and adolescents with IGT, particularly of African-American descent, are at very high risk for developing type 2 diabetes over a short period of time. Parameters derived from an OGTT and not fasting samples can serve as predictors of changes in glucose tolerance.
The Challenge of Achieving National Cholesterol Goals in Patients With Diabetes
Authors: Kennedy Amanda G. , MacLean Charles D. , Littenberg Benjamin , Ades Philip A. , Pinckney Richard G. 
Published: March 2007

OBJECTIVE—This study analyzed lipid results from a large community-based population of patients with diabetes to assess the feasibility of attaining the standard and new optional LDL-based lipid goals using currently available lipid-lowering medications.
RESEARCH DESIGN AND METHODS—Ambulatory patients with diabetes who were interviewed as part of the Vermont Diabetes Information System trial with a reported LDL were analyzed. Patients were categorized into high-risk and very-high-risk cardiovascular status. For patients not at the LDL goal, the required changes in therapy to achieve the goal were assessed.
RESULTS—Of the entire cohort, 49.4% (321 of 650) had LDL &lt;100 mg/dl. According to the National Cholesterol Education Program, 29.4% (191 of 650) of patients were very high risk and have an optional LDL goal of &lt;70 mg/dl. Only 15.7% (30 of 191) of very-high-risk patients had an LDL &lt;70 mg/dl. Based on our analysis of high-risk patients, 17 of 459 (3.7%) would require more than two lipid-lowering drugs to achieve an LDL &lt;100 mg/dl. In the very-high-risk group, we estimate that 26.2% (50 of 191) of patients will not reach LDL &lt;70 mg/dl with two lipid-lowering medications.
CONCLUSIONS—In many patients with diabetes and cardiovascular disease, it will be difficult to attain an LDL goal of &lt;70 mg/dl. Approximately 25% of patients will require more than two lipid-lowering drugs at maximal doses to attain this goal, assuming 100% tolerance of lipid-lowering medications.
One-Hour Postload Plasma Glucose in Middle Age and Medicare Expenditures in Older Age Among Nondiabetic Men and Women
Authors: Liu Kiang , Dyer Alan R. , Vu Thanh-Huyen , Pirzada Amber , Manheim Larry M. , Manning Willard G. , Ashraf Muhammad S. , Garside Daniel B. , Daviglus Martha L. 
Published: March 2007

OBJECTIVE—To examine associations in nondiabetic individuals of 1-h postload plasma glucose measured in young adulthood and middle age with subsequent Medicare expenditures for cardiovascular disease (CVD), diabetes, cancer, and all health care at age 65 years or older using data from the Chicago Heart Association Detection Project in Industry (CHA).
RESEARCH DESIGN AND METHODS—Medicare data (1984–2000) were linked with CHA baseline records (1967–1973) for 8,580 men and 6,723 women ages 33–64 years who were free of coronary heart disease, diabetes, and major electrocardiogram (ECG) abnormalities and who were Medicare eligible (65+ years) for at least 2 years. Participants were classified based on 1-h postload plasma glucose levels &lt;120, 120–199, or ≥200 mg/dl.
RESULTS—With adjustment for baseline age, cigarette smoking, serum cholesterol, systolic blood pressure, BMI, ethnicity, education, and minor ECG abnormalities, the average annual and cumulative Medicare, total, and diabetes- and CVD-related charges were significantly higher with higher baseline plasma glucose in women, while only diabetes-related charges were significantly higher in men. For example, in women, multivariate-adjusted CVD-related cumulative charges were, respectively, $14,260, $18,909, and $21,183 for the three postload plasma glucose categories (P value for trend = 0.035).
CONCLUSIONS—These findings suggest that maintaining low glucose levels early in life has the potential to reduce health care costs in older age.
A Randomized Multicenter Trial Comparing the GlucoWatch Biographer With Standard Glucose Monitoring in Children With Type 1 Diabetes
Authors:   The Diabetes Research in Children Network (DirecNet) Study Group
Published: March 2007

OBJECTIVE—This study assesses whether use of the GlucoWatch G2 Biographer (GW2B) in addition to standard glucose monitoring lowers HbA1c and reduces hypoglycemia compared with standard glucose monitoring alone.
RESEARCH DESIGN AND METHODS—In all, 200 subjects aged 7 to &lt;18 years with type 1 diabetes were randomly assigned at five centers to standard glucose monitoring (usual care) or standard glucose monitoring plus GW2B use for 6 months. Study outcomes included HbA1c values obtained at 6 months and occurrence of severe hypoglycemia.
RESULTS—The mean HbA1c at baseline was 8.0% in both groups; at 6 months, HbA1c was 7.9% in the usual care group and 8.1% in the GW2B group (95% CI for mean reduction in the GW2B group compared with the usual care group −0.4 to 0.1%; P = 0.15). A decrease in HbA1c of ≥0.5% was achieved in 21% of the usual care group and 28% of the GW2B group (P = 0.29). Severe hypoglycemia events occurred in 7% of the GW2B group and in 2% of the usual care group (P = 0.10). In the GW2B group, sensor use declined throughout the study from a mean value of 2.1 times/week in the 1st month to 1.5 times/week in the 6th month. Reasons given for declining use included skin irritation (76%), frequent skips (56%), excessive alarms (47%), and inaccurate readings (33%).
CONCLUSIONS—Use of the GW2B in addition to standard glucose monitoring did not improve glycemic control or reduce the frequency of severe hypoglycemia. Skin reactions and other problems led to decreasing sensor use over time.
Role of the Decrement in Intraislet Insulin for the Glucagon Response to Hypoglycemia in Humans
Authors: Gosmanov Niyaz R. , Szoke Ervin , Israelian Zarmen , Smith Tamar , Cryer Philip E. , Gerich John E. , Meyer Christian 
Published: March 2007

OBJECTIVE—Animal and in vitro studies indicate that a decrease in β-cell insulin secretion, and thus a decrease in tonic α-cell inhibition by intraislet insulin, may be an important factor for the increase in glucagon secretion during hypoglycemia. However, in humans this role of decreased intraislet insulin is still unclear.
RESEARCH DESIGN AND METHODS—We studied glucagon responses to hypoglycemia in 14 nondiabetic subjects on two separate occasions. On both occasions, insulin was infused from 0 to 120 min to induce hypoglycemia. On one occasion, somatostatin was infused from −60 to 60 min to suppress insulin secretion, so that the decrement in intraislet insulin during the final 60 min of hypoglycemia would be reduced. On the other occasion, subjects received an infusion of normal saline instead of the somatostatin.
RESULTS—During the 2nd h of the insulin infusion, when somatostatin or saline was no longer being infused, plasma glucose (∼2.6 mmol/l) and insulin levels (∼570 pmol/l) were comparable in both sets of experiments (both P &gt; 0.4). In the saline experiments, insulin secretion remained unchanged from baseline (−90 to −60 min) before insulin infusion and decreased from 1.20 ± 0.12 to 0.16 ± 0.04 pmol · kg−1 · min−1 during insulin infusion (P &lt; 0.001). However, in the somatostatin experiments, insulin secretion decreased from 1.18 ± 0.12 pmol · kg−1 · min−1 at baseline to 0.25 ± 0.09 pmol · kg−1 · min−1 before insulin infusion so that it did not decrease further during insulin infusion (−0.12 ± 0.10 pmol · kg−1 · min−1, P = 0.26) indicating the complete lack of a decrement in intraislet insulin during hypoglycemia. This was associated with ∼30% lower plasma glucagon concentrations (109 ± 7 vs. 136 ± 9 pg/ml, P &lt; 0.006) and increments in plasma glucagon above baseline (41 ± 8 vs. 67 ± 11 pg/ml, P &lt; 0.008) during the last 15 min of the hypoglycemic clamp. In contrast, increases in plasma growth hormone were ∼70% greater during hypoglycemia after somatostatin infusion (P &lt; 0.007), suggesting that to some extent the increases in plasma glucagon might have reflected a rebound in glucagon secretion.
CONCLUSIONS—These results provide direct support for the intraislet insulin hypothesis in humans. However, the exact extent to which a decrement in intraislet insulin accounts for the glucagon responses to hypoglycemia remains to be established.
Validation of a Novel Screening Device (NeuroQuick) for Quantitative Assessment of Small Nerve Fiber Dysfunction as an Early Feature of Diabetic Polyneuropathy
Authors: Ziegler Dan , Siekierka-Kleiser Ewa , Meyer Bernd , Schweers Michael 
Published: March 2007

OBJECTIVE—To validate a handheld screening device (NeuroQuick) for an early detection of diabetic distal symmetric polyneuropathy (DSP) by quantitative testing of cold sensation based on the wind chill factor (NeuroQuick threshold [NQT]).
RESEARCH DESIGN AND METHODS—NQT was measured on the dorsum of the foot in 160 healthy subjects as well as 60 and 128 diabetic patients without and with DSP, respectively. DSP was diagnosed by a neurological examination, motor and sensory nerve conduction velocity, vibration perception threshold, and warm and cold thermal perception threshold (TPT) (TPT Medoc). In addition, a C-64 Hz tuning fork and TipTherm device were used as screening instruments.
RESULTS—In the diabetic cohort, NQT correlated significantly with all nerve function tests, with the highest correlation coefficients being found on the foot versus Medoc warm TPT (r = 0.618, P &lt; 0.001) and cold TPT (r = 0.529, P &lt; 0.001). Among patients with DSP, NQT was abnormal, whereas Medoc warm TPT was normal in 34%, whereas only 5% showed the opposite constellation (P &lt; 0.05). Likewise, the corresponding percentages for Medoc cold TPT were 32 and 11%, for TipTherm 47 and 2%, and for the tuning fork 29 and 10% (all P &lt; 0.05), whereas no significant differences were noted when comparing NQT with peroneal motor nerve conduction velocity, sural sensory nerve conduction velocity, and malleolar vibration perception threshold. The coefficients of variation for repeated NQT measurements in 41 control and 41 diabetic subjects were 20.4 and 8.5%, respectively.
CONCLUSIONS—The NeuroQuick is a valid and reliable screening tool for quantitative assessment of small nerve fiber dysfunction. This device appears to be more sensitive in detecting early diabetic polyneuropathy than both elaborate thermal testing and screening tests such as the tuning fork.
Glycemic Control Continues to Deteriorate After Sulfonylureas Are Added to Metformin Among Patients With Type 2 Diabetes
Authors: Cook Michael N. , Girman Cynthia J. , Stein Peter P. , Alexander Charles M. , Holman Rury R. 
Published: March 2007

OBJECTIVE—To describe the course and predictors of glycemic control among patients with type 2 diabetes after sulfonylureas (SUs) are added to metformin (MF).
RESEARCH DESIGN AND METHODS—Patients (n = 2,220) treated with MF monotherapy for &gt;90 days before initiating MF plus SU combination therapy between January 1998 and March 2004 were studied in a retrospective analysis of electronic medical records from U.K. primary care practices using the General Practice Research Database. Median glycoslyated hemoglobin A1c (A1C) before and after SU initiation was described, and patient characteristics were evaluated as predictors of time until A1C ≥8.0% or glucose-lowering therapy was intensified (by starting insulin or adding a third oral agent).
RESULTS—At 6 months post-SU initiation, median A1C resumed deteriorating at a somewhat comparable rate to that observed on MF monotherapy. Higher pre-SU A1C, younger age, female sex, shorter diabetes duration, higher serum creatinine, and being an ex-smoker predicted time until A1C ≥8.0% or glucose-lowering therapy was intensified in various analyses. Median A1C was 9.5% when therapy was intensified. A1C ≥8.0% was estimated to occur in 85% of patients 4 years after SU initiation and in 68% 4 years after initially achieving A1C &lt;7% on MF plus SU therapy.
CONCLUSIONS—In this population, glycemic control is improved following the addition of SUs to MF, but deterioration resumes as early as 6 months. The high proportion of patients remaining on MF plus SU therapy despite having A1C ≥8.0% suggests that there are significant barriers to starting insulin or adding a third agent when treatment goals are not achieved with this combination.
Frequency, Severity, and Morbidity of Hypoglycemia Occurring in the Workplace in People With Insulin-Treated Diabetes
Authors: Leckie Alastair M. , Graham Mairi K. , Grant Joan B. , Ritchie Peter J. , Frier Brian M. 
Published: March 2007

OBJECTIVE—Hypoglycemia was examined in regularly employed people with insulin-treated diabetes to ascertain the frequency and consequences of this problem in the workplace.
RESEARCH DESIGN AND METHODS—A prospective 12-month survey of 243 employed people (age range 20–69 years) with insulin-treated diabetes was performed to record the frequency, severity, and morbidity of hypoglycemia occurring at work. Details of hypoglycemic episodes included time of day, place, activity, causation, blood glucose, treatment, and morbidity. Serial HbA1c measurements were recorded.
RESULTS—A total of 1,955 mild (self-treated) episodes of hypoglycemia (8 per person per annum) and 238 severe (requiring external help) episodes (0.98 per person per annum) were recorded. Of the severe hypoglycemic episodes, 148 (62%) occurred at home, 35 (15%) occurred at work in 27 (11%) people (0.14 episodes per person per annum), and 54 (23%) occurred elsewhere; 52% of severe episodes occurred during sleep. Of the severe hypoglycemic episodes reported, adverse events were described in 54 (23%), with 29 losing consciousness (14%), 21 having a seizure (9%), 4 (2%) sustaining a head injury, 5 (2%) suffering another injury, 3 (1%) injuring someone else, and 2 (1%) damaging property. Severe hypoglycemia in the workplace was associated with six episodes of minor soft-tissue injuries.
CONCLUSIONS—In this cohort, severe hypoglycemia in the workplace was uncommon and seldom caused disruption or serious morbidity. On the basis of the frequency and severity of hypoglycemia observed in the present study, restriction of employment opportunities for most people with insulin-treated diabetes may be difficult to justify.
Caffeinated Coffee, Decaffeinated Coffee, and Caffeine in Relation to Plasma C-Peptide Levels, a Marker of Insulin Secretion, in U.S. Women
Authors: Wu Tianying , Willett Walter C. , Hankinson Susan E. , Giovannucci Edward 
Published: March 2007

OBJECTIVE—Coffee consumption is associated with reduced risk of type 2 diabetes, but the mechanism is not clearly understood. Elevated C-peptide, as a marker of insulin secretion, has been linked to insulin-resistant type 2 diabetes. In this study, we examined consumption of caffeinated and decaffeinated coffee and total caffeine in relation to concentrations of plasma C-peptide.
RESEARCH DESIGN AND METHODS—Plasma C-peptide concentrations were measured in a cross-sectional setting among 2,112 healthy women from the Nurses’ Health Study I who provided blood samples in 1989–1990. Consumption of caffeinated and decaffeinated coffee and total caffeine was assessed using a semiquantitative food-frequency questionnaire in 1990.
RESULTS—Intakes of caffeinated and decaffeinated coffee and caffeine in 1990 were each inversely associated with C-peptide concentration in age-adjusted, BMI-adjusted, and multivariable-adjusted analyses. In multivariable analysis, concentrations of C-peptide were 16% less in women who drank &gt;4 cups/day of caffeinated or decaffeinated coffee compared with nondrinkers (P &lt; 0.005 for each). Women in the highest quintile compared with the lowest quintile of caffeine intake had 10% lower C-peptide levels (P = 0.02). We did not find any association between tea and C-peptide. The inverse association between caffeinated coffee and C-peptide was considerably stronger in obese (27% reduction) and overweight women (20% reduction) than in normal weight women (11% reduction) (P = 0.005).
CONCLUSIONS—Our findings suggest a potential reduction of insulin secretion by coffee in women. This reduction may be related to other components in coffee rather than caffeine.
The Effect of Rosiglitazone on Overweight Subjects With Type 1 Diabetes
Authors: Strowig Suzanne M. , Raskin Philip 
Published: March 2007

OBJECTIVE—To evaluate the safety and effectiveness of rosiglitazone in the treatment of overweight subjects with type 1 diabetes.RESEARCH DESIGN AND METHODS—A total of 50 adult type 1 diabetic subjects with a baseline BMI ≥27 kg/m2 were randomly assigned in a double-blind fashion to take insulin and placebo (n = 25) or insulin and rosiglitazone 4 mg twice daily (n = 25) for a period of 8 months. Insulin regimen and dosage were modified in all subjects to achieve near-normal glycemic control.RESULTS—Both groups experienced a significant reduction in HbA1c (A1C) level (rosiglitazone: 7.9 ± 1.3 to 6.9 ± 0.7%, P &lt; 0.0001; placebo: 7.7 ± 0.8 to 7.0 ± 0.9%, P = 0.002) and a significant increase in weight (rosiglitazone: 97.2 ± 11.8 to 100.6 ± 16.0 kg, P = 0.008; placebo: 96.4 ± 12.2 to 99.1 ± 15.0, P = 0.016). Baseline measures of BMI (P = 0.001), total daily insulin dose (P = 0.002), total cholesterol (P = 0.005), HDL cholesterol (P = 0.00l), and LDL cholesterol (P = 0.02) were predictors of improvement in A1C level only in the group treated with rosiglitazone. Total daily insulin dose increased in subjects taking placebo (74.0 ± 33.8 to 82.0 ± 48.9 units, P &lt; 0.05 baseline vs. week 32), but it decreased slightly in subjects taking rosiglitazone (77.5 ± 28.6 to 75.3 ± 33.1 units). Both systolic blood pressure (137.4 ± 15.6 vs. 128.8 ± 14.8 mmHg, baseline vs. week 32, P &lt; 0.02) and diastolic blood pressure (87.2 ± 9.4 vs. 79.4 ± 7.2 mmHg, P &lt; 0.0001) improved in the group treated with rosiglitazone. The total incidence of hypoglycemia did not differ between groups.CONCLUSIONS—Rosiglitazone in combination with insulin resulted in improved glycemic control and blood pressure without an increase in insulin requirements, compared with insulin- and placebo-treated subjects, whose improved glycemic control required an 11% increase in insulin dose. Weight gain and hypoglycemia were similar in both groups at the end of the study. The greatest effect of rosiglitazone occurred in subjects with more pronounced markers of insulin resistance.
Hospitalizations, Nursing Home Admissions, and Deaths Attributable to Diabetes
Authors: Russell Louise B. , Valiyeva Elmira , Roman Sheila H. , Pogach Leonard M. , Suh Dong-Churl , Safford Monika M. 
Published: March 2007

OBJECTIVE—To estimate all-cause hospitalizations, nursing home admissions, and deaths attributable to diabetes using a new methodology based on longitudinal data for a representative sample of older U.S. adults.RESEARCH DESIGN AND METHODS—A simulation model, based on data from the National Health and Nutrition Examination Survey (NHANES) I Epidemiologic Followup Study, was used to represent the natural history of diabetes and control for a variety of baseline risk factors. The model was applied to 6,265 NHANES III adults aged 45–74 years. The prevalence of risk factors in NHANES III, fielded in 1988–1994, better represents today’s adults.RESULTS—For all NHANES III adults aged 45–74 years, a diagnosis of diabetes accounted for 8.6% of hospitalizations, 12.3% of nursing home admissions, and 10.3% of deaths in 1988–1994. For people with diabetes, diabetes alone was responsible for 43.4% of hospitalizations, 52.1% of nursing home admissions, and 47% of deaths. Adjusting for related cardiovascular conditions, which may provide more accurate estimates of attributable risks for people with diabetes, increased these estimates to 51.4, 57.1, and 56.8%, respectively.CONCLUSIONS—Risks of institutionalization and death attributable to diabetes are large. Efforts to translate recent trials of primary prevention into practice and continued efforts to prevent complications of diabetes could have a substantial impact on hospitalizations, nursing home admissions, and deaths and their societal costs.