bluuebunny/crossref_metadata_2025 huggingface dataset:
Lipid Testing Among Patients With Diabetes Who Receive Diabetes Care From Primary Care Physicians
Authors: Massing Mark W. , Henley Nancy S. , Carter-Edwards Lori , Schenck Anna P. , Simpson Ross J.
Published: March 2007

OBJECTIVE—To identify factors related to lipid testing among patients with diabetes who receive diabetes care from primary care physicians.

RESEARCH DESIGN AND METHODS—North Carolina Medicare claims were used to identify individuals with diabetes who received diabetes care from primary care physicians. Lipid testing was related to sociodemographic characteristics, comorbid conditions, physician specialty, and mortality.

RESULTS—Based on Medicare claims from July 1997 through June 1999, 13,660 diabetic North Carolina residents with Medicare, 65–75 years of age, had received HbA1c testing from a single primary care physician during at least three of four consecutive 6-month time intervals. During these 2 years, 31% had no lipid profile and 24% had only one lipid profile. Caucasians were 1.6 times more likely than African Americans to receive lipid profiles. Patients not receiving state Medicare assistance were 1.4 times more likely to have a lipid profile than the presumably lower-income patients receiving assistance. Patients with stroke and heart failure were less likely to receive lipid profiles. Those with no lipid profile were almost twice as likely to die from cardiovascular disease than those with at least two lipid profiles.

CONCLUSIONS—Adherence to lipid testing recommendations by primary care physicians for elderly patients with diabetes has much room for improvement. The most vulnerable patients (African Americans, the economically disadvantaged, and the medically complex) are the least likely to receive lipid testing.
Transfer of Insulin Lispro Across the Human Placenta
Authors: Boskovic Rada , Feig Denice S. , Derewlany Lidia , Knie Brenda , Portnoi Galina , Koren Gideon
Published: March 2007

OBJECTIVE—Insulin lispro (Humalog), a human insulin analog, has a more rapid onset, earlier peak, and shorter duration of glucose lowering activity than regular human insulin. However, it is not known whether insulin lispro crosses the human placenta and reaches the fetus. Therefore, the objective of the present study was to examine whether insulin lispro crosses the placenta using the technique of perfusing a human placental lobule in vitro.

RESEARCH DESIGN AND METHODS—Term human placentae from uncomplicated pregnancies were obtained immediately after delivery. Insulin lispro, at concentrations ranging from 100 to 1000 μU/ml, was introduced into the maternal reservoir. The maternal side of the placenta was perfused with constant concentration of lispro insulin; the fetal circulation was closed. Samples were drawn from both the maternal and fetal circulations at regular intervals. The appearance of insulin lispro in the fetal circulation was analyzed by a specific radioimmunoassay.

RESULTS—No placental transfer of lispro could be detected during perfusion with 100 and 200 μU/ml. In contrast, there was a small concentration-dependent transfer to the fetus at concentrations of 580 μU/ml and higher, detectable after at least an hour of constant concentration of insulin lispro during perfusion. The rate of placental transfer was 0.019 μU · min−1 · g tissue−1 at maternal levels of 580 μU/ml and 0.045 μU · min−1 · g−1 tissue at maternal levels of 1000 μU/ml. Measuring lispro levels in 11 pregnant women revealed that a dose of 50 units may achieve serum concentrations >200 μU/ml with apparent linear correlation between dose and levels.

CONCLUSIONS—Insulin lispro is not likely to cross the placenta at a single standard dose. This study suggests that insulin lispro is unlikely to reach or harm the unborn baby.
Contribution of Plantar Fascia to the Increased Forefoot Pressures in Diabetic Patients
Authors: D’Ambrogi Emanuela , Giurato Laura , D’Agostino Maria Antonietta , Giacomozzi Claudia , Macellari Velio , Caselli Antonella , Uccioli Luigi
Published: March 2007

OBJECTIVES—Secondary to peripheral neuropathy, plantar hyperpressure is a proven risk factor for foot ulceration. But limited joint mobility (LJM) and soft tissue abnormalities may also contribute. The aim of this study was to evaluate the relationships among thickness of plantar fascia, mobility of the metatarso-phalangeal joint, and forces expressed under the metatarsal heads.

RESEARCH DESIGN AND METHODS—We evaluated 61 diabetic patients: 27 without neuropathy (D group), 19 with neuropathy (DN group), and 15 with previous neuropathic foot ulceration (DNPU group). We also examined 21 control subjects (C). Ultrasound evaluation was performed with a high resolution 8- to 10-MHz linear array (Toshiba Tosbee SSA 240). The foot loading pattern was evaluated with a piezo-dynamometric platform. First metatarso-phalangeal joint mobility was assessed with a mechanic goniometer.

RESULTS—Diabetic patients presented increased thickness of plantar fascia (D 2.9 ± 1.2 mm, DN 3.0 ± 0.8 mm, DNPU 3.1 ± 1.0 mm, and C 2.0 ± 0.5.mm; P < 0.05), and significantly reduced motion range at the metatarso-phalangeal joint (D 54.0 ± 29.4°, DN 54.9 ± 17.2°, DNPU 46.8 ± 20.7°, and C 100.0 ± 10.0°; P < 0.05). The evaluation of foot-floor interaction under the metatarsal heads showed increased vertical forces in DN and DNPU and increased medio-lateral forces in DNPU. An inverse correlation was found between the thickness of plantar fascia and metatarso-phalangeal joint mobility (r = −0.53). The thickness of plantar fascia was directly correlated with vertical forces under the metatarsal heads (r = 0.52).

CONCLUSIONS—In diabetic patients, soft tissue involvement may contribute to the increase of vertical forces under the metatarsal heads. Changes in the structure of plantar fascia may also influence the mobility of the first metatarso-phalangeal joint.
Factors Affecting Progression of Renal Failure in Patients With Type 2 Diabetes
Authors: Ueda Hideki , Ishimura Eiji , Shoji Tetsuo , Emoto Masanori , Morioka Tomoaki , Matsumoto Naoki , Fukumoto Shinya , Miki Takami , Inaba Masaaki , Nishizawa Yoshiki
Published: March 2007

OBJECTIVE—Hyperglycemia and hypertension are known to be risk factors for the development of proteinuria in patients with diabetes. Little is known, however, about predictors of progression of renal failure in diabetic patients.

RESEARCH DESIGN AND METHODS—We investigated factors affecting progression of renal failure by measuring the doubling of serum creatinine (s-Cr) as an end point in a cohort of 85 type 2 diabetic patients with chronic renal insufficiency/failure (s-Cr >1.5 and <3.7 mg/dl, 61 ± 11 years old, 51 men and 34 women, mean s-Cr 2.3 ± 0.6 mg/dl).

RESULTS—The survey period (mean ± SD) was 14.2 ± 10.8 months. The cumulative incidence of the end point in patients with insulin therapy (n = 41) was significantly lower than that in patients without it (n = 44) (P = 0.0022, P values by log-rank test). Multivariate Cox analysis revealed insulin therapy (hazard ratio [HR] 0.435, 95% CI 0.252–0.750, P = 0.0027), serum albumin (0.484, 284–0.823, P = 0.0074), mean blood pressure (1.023, 1.004–1.043, P = 0.017), and hemoglobin (0.841, 0.728–0.972, P = 0.0194) to be independent and significant predictors of progression to renal failure, whereas HbA1c or serum cholesterol were not.

CONCLUSION—In type 2 diabetic patients with renal failure, hypoalbuminemia, anemia, higher mean blood pressure, and lack of use of insulin predict rapid progression of renal failure, but HbA1c does not, and insulin therapy may be possibly an indicator of the delay in progression of renal failure.
Battling Insulin Resistance in Elderly Obese People With Type 2 Diabetes
Authors: Willey Karen A. , Singh Maria A. Fiatarone
Published: March 2007

Exercise improves insulin resistance and has beneficial effects in preventing and treating type 2 diabetes. However, aerobic exercise is hindered in many type 2 diabetic patients because of advancing age, obesity, and other comorbid conditions. Weight lifting or progressive resistance training (PRT) offers a safe and effective exercise alternative for these people. PRT promotes favorable energy balance and reduced visceral fat deposition through enhanced basal metabolism and activity levels while counteracting age- and disease-related muscle wasting. PRT improves insulin sensitivity and glycemic control; increases muscle mass, strength, and endurance; and has positive effects on bone density, osteoarthritic symptoms, mobility impairment, self-efficacy, hypertension, and lipid profiles. PRT also alleviates symptoms of anxiety, depression, and insomnia in individuals with clinical depression and improves exercise tolerance in individuals with cardiac ischemic disease and congestive heart failure; all of these aspects are relevant to the care of diabetic elders. Moreover, PRT is safe and well accepted in many complex patient populations, including very frail elderly individuals and those with cardiovascular disease. The greater feasibility of using PRT over aerobic exercise in elderly obese type 2 diabetic individuals because of concomitant cardiovascular, arthritic, and other disease provides a solid rationale for investigating the global benefits of PRT in the management of diabetes.
Changes in Aerobic Capacity and Visceral Fat but not Myocyte Lipid Levels Predict Increased Insulin Action After Exercise in Overweight and Obese Men
Authors: Gan Seng Khee , Kriketos Adamandia D. , Ellis Bronwyn A. , Thompson Campbell H. , Kraegen Edward W. , Chisholm Donald J.
Published: March 2007

OBJECTIVE—To examine the effect of moderate intensity physical activity on the interactions between central abdominal adiposity, myocyte lipid content, and insulin action in overweight and obese, sedentary men.

RESEARCH DESIGN AND METHODS—Myocyte lipid (biochemical triglyceride and long-chain acyl CoA [LCAC] from vastus lateralis biopsy and soleus and tibialis anterior intramyocellular lipid by 1H-magnetic resonance spectroscopy), regional body and abdominal fat (dual-energy X-ray absorptiometry and magnetic resonance imaging), serum lipids, insulin action (hyperinsulinemic-euglycemic clamp), and substrate oxidation were measured in 18 nondiabetic, sedentary, and overweight to obese men (aged 37.4 ± 1.3 years and BMI 30.9 ± 0.7 kg/m2, range 26.4–37.6) at baseline, after the first two to four bouts of aerobic exercise (55–70% of Vo2max for 40 min/session), and at completion of 4.1 ± 0.2 exercise sessions/week for 9.7 ± 0.5 weeks (postexercise measurements performed 24–36 h after the last exercise bout).

RESULTS—Mean whole body insulin-stimulated glucose uptake and basal fat oxidation rate increased 16 and 41%, respectively, after two to four bouts of exercise, without further increase at program end. Mean aerobic capacity increased 11%, and central abdominal fat decreased 5% at program end, but myocyte lipid levels were not significantly changed. Posttraining increases in insulin-stimulated glucose uptake were predicted by increase in aerobic capacity (r = 0.726, P = 0.001) and magnitude of reduction in visceral fat (r = −0.544, P = 0.02) and not by changes in myocyte lipid or LCAC levels.

CONCLUSIONS—These results suggest that in overweight and obese sedentary men, increase in insulin sensitivity with moderate intensity exercise is predicted by improvement in aerobic capacity and reduction in visceral fat but is independent of myocyte triglyceride or LCAC levels.
A Randomized Clinical Trial Comparing Breakfast, Dinner, or Bedtime Administration of Insulin Glargine in Patients With Type 1 Diabetes
Authors: Hamann Andreas , Matthaei Stephan , Rosak Christoph , Silvestre Louise ,   for the HOE901/4007 Study Group
Published: March 2007

OBJECTIVE—Insulin glargine (Lantus), a long-acting human insulin analog, provides effective glycemic control when administered at bedtime. This open-label, randomized, parallel group, multicenter study investigated whether insulin glargine is equally effective if administered before breakfast, before dinner, or at bedtime.

RESEARCH DESIGN AND METHODS—Patients with type 1 diabetes on basal-bolus therapy (n = 378, 18–68 years, HbA1c 5.5–9.8%) were treated with once-daily individually titrated insulin glargine in combination with prandial insulin lispro for 24 weeks.

RESULTS—Baseline characteristics were similar in the three groups (overall age 40.9 ± 11.9 years, diabetes duration 17.3 ± 11.5 years). Median total daily insulin dose was similar at baseline (0.65, 0.65, and 0.66 IU/kg for breakfast, dinner, and bedtime, respectively) and remained relatively constant over the study period; however, the insulin glargine–to–total insulin dose ratio increased more in the breakfast group than in the dinner and bedtime groups. A similar reduction of adjusted mean HbA1c from baseline to end point occurred in all patients (7.6–7.4, 7.6–7.5, and 7.6–7.5% for breakfast, dinner, and bedtime, respectively), and a similar percentage achieved HbA1c <7.0% at end point in all groups (29.5, 29.8, and 25.8%, respectively). The 24-h blood glucose profiles in relation to injection time were similar in all groups. The incidences of total symptomatic and severe hypoglycemia did not differ between the three treatment groups; however, nocturnal hypoglycemia occurred in significantly fewer patients in the breakfast group (59.5%) compared with the dinner (71.9%) and bedtime (77.5%) groups (P = 0.005).

CONCLUSIONS—These data suggest that insulin glargine, in combination with insulin lispro, is safe and effective when administered before breakfast, before dinner, or at bedtime.
Prevalence and Major Risk Factors of Reduced Flow Volume in Lower Extremities With Normal Ankle-Brachial Index in Japanese Patients With Type 2 Diabetes
Authors: Suzuki Eiji , Egawa Katsuya , Nishio Yoshihiko , Maegawa Hiroshi , Tsuchiya Masanobu , Haneda Masakazu , Yasuda Hitoshi , Morikawa Shigehiro , Inubushi Toshiro , Kashiwagi Atsunori
Published: March 2007

OBJECTIVE—To clarify the prevalence and major risk factors of reduced flow volume in lower extremities with normal ankle-brachial index (ABI) in Japanese patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS—We recruited 208 consecutive type 2 diabetic patients and 33 age-matched nondiabetic subjects (control group) admitted to our hospital. Thirty-two of the patients had low ABI (<0.90) and intermittent claudication (peripheral arterial disease [PAD] group), and 176 patients had normal ABI (>0.9) (non-PAD group). We evaluated flow volume and resistive index, as an index of arterial resistance to blood flow, at the popliteal artery using gated two-dimensional cine-mode phase-contrast magnetic resonance imaging.

RESULTS—Simple linear regression analysis showed a negative correlation between resistive index and total flow volume in the non-PAD group (r = −0.714, P < 0.001). We defined the means ± 2 SD of these parameters in the control group as the normal range; abnormal resistive index was >1.017, and abnormal flow volume was <50.8 ml/min. The non-PAD group was divided according to the levels of these parameters: 80 patients had both normal resistive index and normal flow volume (normal group); of 96 patients with higher resistive index, 63 had normal flow volume (borderline group) and 33 had reduced flow volume (reduced group). Multiple regression analysis demonstrated that the major risk factors for reduced flow volume were age, hypertension, and diabetic nephropathy (r2 = 0.303, P < 0.001).

CONCLUSIONS—The prevalence of patients without PAD with reduced flow volume in the lower extremities was 16% (n = 33) and comparable with that of patients with PAD with intermittent claudication (n = 32), suggesting that increase in arterial resistance to blood flow may be one of the major causes of lower extremity arterial disease in Japan.
Correlation Between Midthigh Low- Density Muscle and Insulin Resistance in Obese Nondiabetic Patients in Korea
Authors: Kim Dolmi , Nam Suyoun , Ahn Chulwoo , Kim Kyungwook , Yoon Soojee , Kim Junuh , Cha Bongsoo , Lim Sungkil , Kim Kyungrae , Lee Hyunchul , Huh Kapbum
Published: March 2007

OBJECTIVE—We investigated the link between lipid-rich skeletal muscle, namely low-density muscle, and insulin resistance in Korea.

RESEARCH DESIGN AND METHODS—Abdominal adipose tissue areas and midthigh skeletal muscle areas of 75 obese nondiabetic subjects (23 men, 52 women; mean age ± SD, 41.9 ± 14.1 years) were measured by computed tomography (CT). The midthigh skeletal muscle areas were subdivided into low-density muscle (0 to +30 Hounsfield units) and normal-density muscle (+31 to +100 Hounsfield units). The homeostasis model assessment (HOMA) score was calculated to assess whole-body insulin sensitivity.

RESULTS—The abdominal visceral fat area and the midthigh low-density muscle area were found to be well correlated with the HOMA score (r = 0.471, P < 0.01 and r = 0.513, P < 0.01, respectively). The correlation between low-density muscle area and insulin resistance persisted after adjusting for BMI or total body fat mass (r = 0.451, P < 0.01 and r = 0.522, P < 0.01, respectively) and even after adjusting for abdominal visceral fat area (r = 0.399, P < 0.01).

CONCLUSIONS—The midthigh low-density muscle area seems to be a reliable determinant of insulin resistance in Korean obese nondiabetic patients.
Association Between Serum Testosterone Concentration and Carotid Atherosclerosis in Men With Type 2 Diabetes
Authors: Fukui Michiaki , Kitagawa Yoshihiro , Nakamura Naoto , Kadono Mayuko , Mogami Shinichi , Hirata Chizuko , Ichio Naoko , Wada Katsuya , Hasegawa Goji , Yoshikawa Toshikazu
Published: March 2007

OBJECTIVE—There is evidence to suggest that low concentrations of testosterone are associated with an increased risk of cardiovascular disease in men. The aim of this study was to evaluate the relationship between serum testosterone concentration and carotid atherosclerosis as well as major cardiovascular risk factors in men with type 2 diabetes.

RESEARCH DESIGN AND METHODS—Serum free and total testosterone concentrations were measured in 253 consecutive men with type 2 diabetes. The relationships between serum testosterone concentration and carotid atherosclerosis, determined by ultrasonographically evaluated intima-media thickness (IMT) and plaque score (PS) in a subgroup of 154 diabetic patients, as well as major cardiovascular risk factors, including age, blood pressure, and lipid concentrations, were evaluated.

RESULTS—Inverse correlations were found between free testosterone (F-tes) concentration and IMT (r = −0.206, P = 0.0103) and between F-tes concentration and PS (r = −0.334, P < 0.001). The IMT and PS were significantly greater in patients with lower concentrations of F-tes (<10 pg/ml) than in patients with higher concentrations of F-tes (1.01 ± 0.29 vs. 0.91 ± 0.26 mm, P = 0.038; 4.5 ± 3.8 vs. 2.4 ± 3.2, P = 0.0003; respectively). An inverse correlation was found between serum F-tes concentration and age (r = −0.420, P < 0.0001). A positive correlation was found between serum F-tes and total cholesterol concentrations (r = 0.145, P = 0.0238).

CONCLUSIONS—Serum F-tes concentration is inversely associated with carotid atherosclerosis determined by ultrasonographically evaluated IMT and PS in men with type 2 diabetes.
Comparison of Insulin Aspart and Lispro
Authors: Homko Carol , Deluzio Antonio , Jimenez Carolyn , Kolaczynski Jerzy W. , Boden Guenther
Published: March 2007

OBJECTIVE—To compare insulin levels and actions in patients with type 1 diabetes after subcutaneous injection of the rapid-acting insulin analogs aspart and lispro.

RESEARCH DESIGN AND METHODS—Seven C-peptide–negative patients with type 1 diabetes (two men and five women) were studied at the General Clinical Research Center at Temple University Hospital two times, 1 month apart. Their plasma glucose was normalized overnight by intravenous infusion of insulin. The next morning, they received subcutaneous injections of either aspart or lispro (9.4 ± 1.9 U) in random order. For the next 4–5 h, their plasma glucose was clamped at ∼5.5 mmol/l with a variable infusion of 20% glucose. The study was terminated after 8 h.

RESULTS—Both insulin analogs produced similar serum insulin levels (250–300 pmol/l) at ∼30 min and disappeared from serum after ∼4 h. Insulin aspart and lispro had similar effects on glucose and fat metabolism. Effects on carbohydrate metabolism (glucose uptake, glucose oxidation, and endogenous glucose production) peaked after ∼2–3 h and disappeared after ∼5–6 h. Effects on lipid metabolism (plasma free fatty acid, ketone body levels, and free fatty acid oxidation) appeared to peak earlier (at ∼2 h) and disappeared earlier (after ∼4 h) than the effects on carbohydrate metabolism.

CONCLUSIONS—We conclude that both insulin aspart and lispro are indistinguishable from each other with respect to blood levels and that they are equally effective in correcting abnormalities in carbohydrate and fat metabolism in patients with type 1 diabetes.
Predicting Impaired Glucose Tolerance Using Common Clinical Information
Authors: Nelson Karin M. , Boyko Edward J.
Published: March 2007

OBJECTIVE—To develop a score to predict impaired glucose tolerance (IGT) using common clinical data.

RESEARCH DESIGN AND METHODS—We analyzed data from the Third National Health and Nutrition Examination Survey (NHANES III) for 2,746 individuals aged 40–74 years who completed an oral glucose tolerance test. IGT was defined as a 2-h postchallenge glucose ≥140 mg/dl (7.7 mmol/l). We performed bivariate and multivariate analyses to describe the association of IGT with commonly available clinical information. A numerical score to predict IGT was derived from the results of the multivariate logistic regression models.

RESULTS—Fasting glucose levels between 101 and 109 mg/dl (5.6 and 6.0 mmol/l) or between 110 and 125 mg/dl (6.1 and 6.9 mmol/l) were associated with IGT (odds ratio 1.8 and 6.2, respectively; P < 0.05). BMI ≥25 kg/m2, Mexican-American ethnicity, age between 60 and 74 years, hypertension, and triglyceride level ≥150 mg/dl (1.69 mmol/l) were also associated with IGT. The area under the receiver operating characteristic curve for an 8-point scale derived from the multivariate analysis was 0.74 (95% CI 0.72–0.76). Setting a low cut point of 2 on this scale resulted in high sensitivity (86%), whereas a high cut point of 6 yielded high specificity (97%) for the detection of IGT.

CONCLUSIONS—A numerical score based on common clinical data can identify individuals with a low or high likelihood of having IGT.
Efficacy and Safety of Combination Therapy
Authors: Raskin Philip , Klaff Leslie , McGill Janet , South Stephen A. , Hollander Priscilla , Khutoryansky Naum , Hale Paula M. ,   Repaglinide vs. Nateglinide Metformin Combination Study Group
Published: March 2007

OBJECTIVE—An open-label, parallel-group, randomized, multicenter trial was conducted to compare efficacy and safety of repaglinide versus nateglinide, when used in a combination regimen with metformin for treatment of type 2 diabetes.

RESEARCH DESIGN AND METHODS—Enrolled patients (n = 192) had HbA1c >7% and ≤12% during previous treatment with a sulfonylurea, metformin, or low-dose Glucovance (glyburide ≤2.5 mg, metformin ≤500 mg). After a 4-week metformin run-in therapy period (doses escalated to 1,000 mg b.i.d.), patients were randomized to addition of repaglinide (n = 96) (1 mg/meal, maximum 4 mg/meal) or nateglinide (n = 96) (120 mg/meal, reduced to 60 mg if needed) to the regimen for 16 weeks. Glucose, insulin, and glucagon were assessed after a liquid test meal at baseline and week 16.

RESULTS—Final HbA1c values were lower for repaglinide/metformin treatment than for nateglinide/metformin (7.1 vs. 7.5%). Repaglinide/metformin therapy showed significantly greater mean reductions of HbA1c (−1.28 vs. −0.67%; P < 0.001) and of fasting plasma glucose (FPG) (−39 vs. −21 mg/dl; P = 0.002). Self-monitoring of blood glucose profiles were significantly lower for repaglinide/metformin before breakfast, before lunch, and at 2:00 a.m. Changes in the area under the curve of postprandial glucose, insulin, or glucagon peaks after a test meal were not significantly different for the two treatment groups during this study. Median final doses were 5.0 mg/day for repaglinide and 360 mg/day for nateglinide. Safety assessments were comparable for the two regimens.

CONCLUSIONS—The addition of repaglinide to metformin therapy resulted in reductions of HbA1c and FPG values that were significantly greater than the reductions observed for addition of nateglinide.
Etiological Investigation of Diabetes in Young Adults Presenting With Apparent Type 2 Diabetes
Authors: Owen Katharine R. , Stride Amanda , Ellard Sian , Hattersley Andrew T.
Published: March 2007

OBJECTIVE—Young adults with newly diagnosed apparent type 2 diabetes present the clinician with a wide differential diagnosis of possible etiology, including autoimmune and genetic causes as well as young-onset type 2 diabetes (YT2D). The characteristics of these groups have been described, but it is not known in which subjects investigation for etiology may be beneficial.

RESEARCH DESIGN AND METHODS—A total of 268 unselected U.K. Caucasian subjects diagnosed at ages 18–45 years and not treated with permanent insulin for ≤6 months were studied. All subjects underwent clinical assessment and screening for GAD antibodies (GADA) and tyrosine phosphatase IA-2 antibodies (IA-2A). Screening for a common mutation in the hepatocyte nuclear factor-1α (HNF-1α) gene and the common mitochondrial mutation was performed in the antibody-negative subjects. Subjects without insulin resistance were selected for sequencing of the HNF-1α gene.

RESULTS—A specific etiology was defined in 11.6% of the 268 subjects and in 24.7% of the lean subjects. Twenty-six subjects (9.7%) were positive for a β-cell antibody, one subject had familial partial lipodystrophy and the lamin A/C mutation R482W, and two subjects had the mitochondrial mutation A3243G. Two of 15 selected subjects had HNF-1α mutations, the novel missense mutation A501T, and the previously reported R583Q.

CONCLUSIONS—This unselected series shows that there is considerable heterogeneity in apparent YT2D. β-Cell autoantibodies should be performed in all those presenting at ages 18–45 years. Genetic investigations can be targeted to phenotypically defined subjects. The finding of a specific etiology will allow individualization of management and give patients valuable information about their condition.
Reduced Skeletal Muscle Oxygen Uptake and Reduced β-Cell Function
Authors: Thamer Claus , Stumvoll Michael , Niess Andreas , Tschritter Otto , Haap Michael , Becker Regine , Shirkavand Fatemeh , Bachmann Oliver , Rett Kristian , Volk Annette , Häring Hans , Fritsche Andreas
Published: March 2007

OBJECTIVE—Studies on insulin sensitivity and insulin secretion in subjects with a familial predisposition for type 2 diabetes mellitus (T2DM) traditionally produce inconsistent results. This may be due to small sample size, subject selection, matching procedures, and perhaps lack of a measure of physical fitness.

RESEARCH DESIGN AND METHODS—In the present study, we specifically tested the hypothesis that a family history of T2DM is associated with reduced Vo2max, measured by incremental bicycle ergometry, independent of insulin sensitivity estimated from an oral glucose tolerance test (OGTT; n = 424) and measured by a euglycemic-hyperinsulinemic clamp (n = 185). Subjects included in the study were young (34 ± 10 years), healthy, and normal glucose tolerant with either a first-degree relative (FDR) with T2DM (n = 183), a second-degree relative with T2DM (n = 94), or no family history of T2DM (control subjects, n = 147). BMI, percent body fat, waist-to-hip ratio (WHR), and habitual physical activity (HPA; standard questionnaire) were comparable among groups. FDRs had significantly lower Vo2max than control subjects: 40.5 ± 0.6 vs. 45.2 ± 0.9 ml O2/kg lean body mass, P = 0.01 after adjusting for sex, age, BMI, HPA, and insulin sensitivity (euglycemic-hyperinsulinemic clamp).

RESULTS—BMI, percent body fat, waist-to-hip ratio (WHR), and habitual physical activity (HPA; standard questionnaire) were comparable among groups. FDRs had significantly lower Vo2max than control subjects: 40.5 ± 0.6 vs. 45.2 ± 0.9 ml O2/kg lean body mass, P = 0.01 after adjusting for sex, age, BMI, HPA, and insulin sensitivity (euglycemic-hyperinsulinemic clamp). Insulin sensitivity per se was not affected by family history of T2DM after adjusting for age, sex, BMI, and percent body fat (P = 0.76). The appropriateness of β-cell function for the individual insulin sensitivity (disposition index: product of a validated secretion parameter [OGTT] and sensitivity [clamp]) was significantly lower in FDRs (87 ± 4 units) versus control subjects (104 ± 6 units, P = 0.02 after adjusting for sex, age, and BMI). Analyses of the larger OGTT group produced essentially the same results.

CONCLUSIONS—In conclusion, these data are compatible with the hypothesis that familial predisposition for T2DM impairs maximal oxygen consumption in skeletal muscle. Because habitual physical activity was not different, genetic factors may be involved. Conceivably, reduced Vo2max precedes skeletal muscle insulin resistance, providing a partial explanation for discrepancies in the literature.
The Platelet in Diabetes
Authors: Colwell John A. , Nesto Richard W.
Published: March 2007

Accelerated atherosclerosis and the increased risk of thrombotic vascular events in diabetes may result from dyslipidemia, endothelial dysfunction, platelet hyperreactivity, an impaired fibrinolytic balance, and abnormal blood flow. There is also a correlation between hyperglycemia and cardiovascular (CV) events. The importance of platelets in the atherothrombotic process has led to investigation of using antiplatelet agents to reduce CV risk. A meta-analysis conducted by the Antiplatelet Trialists’ Collaboration demonstrated that aspirin reduced the risk of ischemic vascular events as a secondary prevention strategy in numerous high-risk groups, including patients with diabetes. Based on results from placebo-controlled randomized trials, the American Diabetes Association recommends low-dose enteric-coated aspirin as a primary prevention strategy for people with diabetes at high risk for CV events. Clopidogrel is recommended if aspirin allergy is present. There is occasionally a need for an alternative to aspirin or for additive antiplatelet therapy. Aspirin in low doses inhibits thromboxane production by platelets but has little to no effect on other sites of platelet reactivity. Agents such as ticlopidine and clopidogrel inhibit ADP-induced platelet activation, whereas the platelet glycoprotein (Gp) IIb/IIIa complex receptor antagonists block activity at the fibrinogen binding site on the platelet. These agents appear to be useful in acute coronary syndromes (ACSs) in diabetic and nondiabetic patients. A combination of clopidogrel plus aspirin was more effective than placebo plus standard therapy (including aspirin) in reducing a composite CV outcome in patients with unstable angina and non-ST segment elevation myocardial infarction. In a meta-analysis of six trials in diabetic patients with ACSs, intravenous GpIIb-IIIa inhibitors reduced 30-day mortality when compared with control subjects. Results from controlled prospective clinical trials justify the use of enteric-coated low-dose aspirin (81–325 mg) as a primary or secondary prevention strategy in adult diabetic individuals (aged >30 years) at high risk for CV events. Recent studies support the use of clopidogrel in addition to standard therapy, as well as the use of GpIIb-IIIa inhibitors in ACS patients.
Impaired Fasting Glucose and Impaired Glucose Tolerance in Women With Prior Gestational Diabetes Are Associated With a Different Cardiovascular Profile
Authors: Pallardo Luis Felipe , Herranz Lucrecia , Martin-Vaquero Pilar , Garcia-Ingelmo Teresa , Grande Cristina , Jañez Mercedes
Published: March 2007

OBJECTIVE—The purpose of this study was to investigate the association of cardiovascular risk factors to impaired glucose tolerance (IGT) and to impaired fasting glucose (IFG) in women with prior gestational diabetes mellitus (GDM).

RESEARCH DESIGN AND METHODS—We studied 838 women with prior GDM. Postpartum glucose tolerance status was classified as normal, IFG, IGT, IFG plus IGT, and diabetes according to the World Health Organization criteria. Postpartum BMI, waist circumference, blood pressure, triglyceride, cholesterol, and HDL cholesterol were assessed.

RESULTS—BMI and blood pressure were significantly higher in women with IFG than in women with normal glucose status. BMI and waist circumference were significantly higher in women with IFG plus IGT than in women with normal glucose status. No differences were observed between women with IGT and normal glucose status. The prevalence of hypertension and obesity was significantly increased in IFG compared with normal glucose status. The prevalence of obesity and abnormal lipids was significantly increased in IFG plus IGT compared with normal glucose status. IGT showed no increased prevalence of cardiovascular risk factors.

CONCLUSIONS—Traditional cardiovascular risk factors have a stronger association with isolated IFG than with isolated IGT in women with prior GDM.
Quantitative Insulin Sensitivity Check Index and the Reciprocal Index of Homeostasis Model Assessment in Normal Range Weight and Moderately Obese Type 2 Diabetic Patients
Authors: Yokoyama Hisayo , Emoto Masanori , Fujiwara Shigehiko , Motoyama Koka , Morioka Tomoaki , Komatsu Miyoko , Tahara Hideki , Shoji Tetsuo , Okuno Yasuhisa , Nishizawa Yoshiki
Published: March 2007

OBJECTIVE—To investigate whether the quantitative insulin sensitivity check index (QUICKI) and the reciprocal index of homeostasis model assessment (1/HOMA-IR) derived from fasting plasma glucose and insulin level are excellent surrogate indices of insulin resistance in both normal range-weight and moderately obese type 2 diabetic and healthy subjects.

RESEARCH DESIGN AND METHODS—The association between QUICKI or 1/HOMA-IR and insulin resistance index assessed by euglycemic-hyperinsulinemic clamp (clamp-IR) was investigated in 121 type 2 diabetic and 29 healthy subjects recruited from among 120 (age 55 ± 11, 48 ± 15, and 52 ± 15 years [means ± SD], respectively). Type 2 diabetic subjects were divided into groups of 76 normal range-weight and 45 moderately obese subjects (BMI 21.4 ± 2.3 vs. 27.2 ± 2.2 kg/m2, P < 0.0001).

RESULTS—QUICKI and 1/HOMA-IR were significantly lower in the moderately obese group than in the normal range-weight type 2 diabetic and healthy groups (n = 120) (QUICKI, 0.338 ± 0.030, 0.371 ± 0.037, and 0.389 ± 0.041, respectively, P < 0.0001; 1/HOMA-IR, 0.50 ± 0.33, 0.92 ± 0.55, and 1.24 ± 0.82, P < 0.0001). QUICKI was strongly correlated with clamp-IR in normal range-weight, moderately obese type 2 diabetic, and healthy subjects (r = 0.641, 0.570, and 0.502, respectively; all subjects, r = 0.608, P < 0.01) and 1/HOMA-IR exhibited correlations comparable to those of QUICKI with clamp-IR (r = 0.637, 0.530, and 0.461, respectively; all subjects, r = 0.589, P < 0.001). In multiple regression models including QUICKI or 1/HOMA-IR as an independent variable, the estimation formula accounted for 55% of the variability of clamp-IR for the group of all type 2 diabetic subjects (R2 = 0.547 and 0.551, respectively, P ≤ 0.0001).

CONCLUSIONS—QUICKI and 1/HOMA-IR were highly correlated with clamp-IR, with comparable coefficients in both normal range-weight and moderately obese type 2 diabetic patients and nondiabetic subjects. The latter can probably be applied clinically in view of its convenience.
One-Year Outcome of a Combination of Weight Loss Therapies for Subjects With Type 2 Diabetes
Authors: Redmon J. Bruce , Raatz Susan K. , Reck Kristell P. , Swanson Joyce E. , Kwong Christine A. , Fan Qiao , Thomas William , Bantle John P.
Published: March 2007

OBJECTIVE—The purpose of this study was to evaluate the effects of a combination weight loss program using intermittent low-calorie diets, energy-controlled meal replacement products, and sibutramine on weight loss, diabetes control, and cardiovascular risk factors in overweight or obese subjects with type 2 diabetes.

RESEARCH DESIGN AND METHODS—Overweight or obese individuals with type 2 diabetes treated with diet or oral medication were randomly assigned to either a standard therapy or combination therapy group. Both groups received a standardized program to facilitate weight loss. The combination therapy group also received 10–15 mg sibutramine daily, low-calorie diets using meal replacement products for 1 week every 2 months, and between low-calorie diet weeks, once daily use of meal replacement product and snack bars to replace one usual meal and snack. Primary outcome measures were changes in body weight, glycemic control, plasma lipids, blood pressure, pulse, and body composition at 1 year.

RESULTS—At 1 year, combination therapy, compared with standard therapy, resulted in significantly more weight loss (−7.3 ± 1.3 kg vs. −0.8 ± 0.9 kg, P < 0.001) and reduction in HbA1c (−0.6 ± 0.3 vs. 0.0 ± 0.2%, P = 0.05). Combination therapy resulted in reduced requirement for diabetes medications and decreased fat mass and lean body mass. A 5-kg decrease in weight at 1 year was associated with a decrease of 0.4% in HbA1c (P = 0.006). Changes in fasting glucose, lipids, pulse, and blood pressure did not differ between groups.

CONCLUSIONS—This combination weight loss program resulted in greater weight loss and improved diabetes control compared with a standard weight loss program in overweight or obese subjects with type 2 diabetes.
The Development and Validation of a Neuropathy- and Foot Ulcer-Specific Quality of Life Instrument
Authors: Vileikyte Loretta , Peyrot Mark , Bundy Christine , Rubin Richard R. , Leventhal Howard , Mora Pablo , Shaw Jonathan E. , Baker Paul , Boulton Andrew J.M.
Published: March 2007

OBJECTIVE—The purpose of this study was to develop a questionnaire that measures patients’ perceptions of the impact of diabetic peripheral neuropathy and foot ulcers on their quality of life and to assess the psychometric properties of this instrument in a sample of patients with varying severity and symptomatology of diabetic peripheral neuropathy.

RESEARCH DESIGN AND METHODS—The neuropathy- and foot ulcer-specific quality of life instrument (NeuroQoL), generated from interviews with patients with (n = 47) and without (n = 15) diabetic peripheral neuropathy, was administered to 418 consecutive patients with diabetic peripheral neuropathy (35% with foot ulcer history) attending either U.K. (n = 290) or U.S. (n = 128) diabetes centers. Psychometric tests of NeuroQoL included factor analyses and internal consistency of scales; a series of multivariate analyses were performed to establish its criterion, construct, and incremental validity. Results were compared with those obtained using the Short Form (SF)-12 measure of health-related functioning.

RESULTS—Factor analyses of NeuroQoL revealed three physical symptom measures and two psychosocial functioning measures with good reliability (α = 0.86–0.95). NeuroQoL was more strongly associated with measures of neuropathic severity than SF-12, more fully mediated the relationship of diabetic peripheral neuropathy with overall quality of life, and significantly increased explained variance in overall quality of life over SF-12.

CONCLUSIONS—NeuroQoL reliably captures the key dimensions of the patients’ experience of diabetic peripheral neuropathy and is a valid tool for studying the impact of neuropathy and foot ulceration on quality of life.
Haptoglobin Genotype Is Predictive of Major Adverse Cardiac Events in the 1-Year Period After Percutaneous Transluminal Coronary Angioplasty in Individuals With Diabetes
Authors: Roguin Ariel , Koch Werner , Kastrati Adnan , Aronson Doron , Schomig Albert , Levy Andrew P.
Published: March 2007

OBJECTIVE—The goal of this study was to determine whether the haptoglobin (Hp) genotype was predictive of restenosis and major adverse cardiac events (MACEs) after percutaneous transluminal coronary angioplasty (PTCA) in individuals with diabetes.

RESEARCH DESIGN AND METHODS—A consecutive series of 935 diabetic patients treated with oral agents and/or insulin were followed for 1 year after PTCA. The primary study end point was angiographic restenosis, MACEs and secondary study end points were defined as target vessel revascularization, myocardial infarction, and death. Two alleles exist at the Hp gene locus, denoted 1 and 2. The Hp genotype (Hp 1–1, Hp 2–1, or Hp 2–2) was determined by PCR.

RESULTS—In multivariate analysis controlling for all known determinants of outcome after PTCA, we found that the Hp genotype was a highly significant independent predictor of MACEs in the 1-year period after PTCA in individuals with diabetes. This was predominantly due to differences in the risk of myocardial infarction during that period: Hp 1–1, 0 of 129 (0%); Hp 2–1, 20 of 424 (4.7%); and Hp 2–2, 32 of 382 (8.4%); P < 0.0001.

CONCLUSIONS—The Hp genotype seems to be highly predictive of adverse cardiac events, particularly myocardial infarction, in the 1-year period after PTCA. Determination of the Hp genotype may be useful in the evaluation of new therapies to reduce cardiovascular risk after PTCA.
Restoration of Sensation, Reduced Pain, and Improved Balance in Subjects With Diabetic Peripheral Neuropathy
Authors: Leonard David R. , Farooqi M. Hamed , Myers Sara
Published: March 2007

OBJECTIVE—Diabetic peripheral neuropathy (DPN) has been thought to be progressive and irreversible. Recently, symptomatic reversal of DPN was reported after treatments with a near-infrared medical device, the Anodyne Therapy System (ATS). However, the study was not controlled nor was the investigator blinded. We initiated this study to determine whether treatments with the ATS would decrease pain and/or improve sensation diminished due to DPN under a sham-controlled, double-blind protocol.

RESEARCH DESIGN AND METHODS—Tests involved the use of the 5.07 and 6.65 Semmes Weinstein monofilament (SWM) and a modified Michigan Neuropathy Screening Instrument (MNSI). Twenty-seven patients, nine of whom were insensitive to the 6.65 SWM and 18 who were sensitive to this filament but insensitive to the 5.07 SWM, were studied. Each lower extremity was treated for 2 weeks with sham or active ATS, and then both received active treatments for an additional 2 weeks.

RESULTS—The group of 18 patients who could sense the 6.65 SWM but were insensitive to the 5.07 SWM at baseline obtained a significant decrease in the number of sites insensate after both 6 and 12 active treatments (P < 0.02 and 0.001). Sham treatments did not improve sensitivity to the SWM, but subsequent active treatments did (P < 0.002). The MNSI measures of neuropathic symptoms decreased significantly (from 4.7 to 3.1; P < 0.001). Pain reported on the 10-point visual analog scale decreased progressively from 4.2 at entry to 3.2 after 6 treatments and to 2.3 after 12 treatments (both P < 0.03). At entry, 90% of subjects reported substantial balance impairment; after treatment, this decreased to 17%. However, among the group of nine patients with greater sensory impairment measured by insensitivity to the 6.65 SWM at baseline, improvements in sensation, neuropathic symptoms, and pain reduction were not significant.

CONCLUSIONS—ATS treatments improve sensation in the feet of subjects with DPN, improve balance, and reduce pain.
Nonalbuminuric Renal Insufficiency in Type 2 Diabetes
Authors: MacIsaac Richard J. , Tsalamandris Con , Panagiotopoulos Sianna , Smith Trudy J. , McNeil Karen J. , Jerums George
Published: March 2007

OBJECTIVE—To determine the prevalence and characteristics of patients with type 2 diabetes who have impaired renal function, defined as a glomerular filtration rate (GFR) <60 ml · min−1 · 1.73 m−2, and normoalbuminuria.

RESEARCH DESIGN AND METHODS—A cross-sectional survey of 301 outpatients attending a single tertiary referral center using the plasma disappearance of isotopic 99mTc-diethylene-triamine-penta-acetic acid to measure GFR and at least two measurements of urinary albumin excretion rate (AER) over 24 h to determine albuminuria.

RESULTS—A total of 109 patients (36%) had a GFR <60 ml · min−1 · 1.73 m−2. The overall prevalence of normo-, micro-, and macroalbuminuria was 43 of 109 (39%), 38 of 109 (35%), and 28 of 109 (26%), respectively. Compared with patients with macroalbuminuria, those with normoalbuminuria were more likely to be older and female. After excluding patients whose normoalbuminuric status was possibly related to the initiation of a renin-angiotensin system (RAS) inhibitor before the start of the study, the prevalence of a GFR <60 ml · min−1 · 1.73 m−2 and normoalbuminuria was 23%. Temporal changes in GFR in a subset of 34 of 109 (32%) unselected patients with impaired renal function were available for comparison over a 3- to 10-year period. The rates of decline in GFR (ml · min−1 · 1.73 m−2 · year−1) of −4.6 ± 1.0, −2.8 ± 1.0, and −3.0 ± 07 were not significantly different for normo- (n = 12), micro- (n = 12), and macroalbuminuric (n = 10) patients, respectively.

CONCLUSIONS—These results suggest that patients with type 2 diabetes can commonly progress to a significant degree of renal impairment while remaining normoalbuminuric.
Prognostic Value of Epicardial Coronary Artery Constriction to the Cold Pressor Test in Type 2 Diabetic Patients With Angiographically Normal Coronary Arteries and No Other Major Coronary Risk Factors
Authors: Nitenberg Alain , Valensi Paul , Sachs Régis , Cosson Emmanuel , Attali Jean-Raymond , Antony Isabelle
Published: March 2007

OBJECTIVE—Endothelium-dependent coronary dilation is impaired in diabetic patients and has been found to independently predict cardiovascular events (CVEs) in patients with multiple coronary risk factors. The aim of this study was to evaluate the outcome of type 2 diabetic patients on the basis of epicardial coronary dysfunction.

RESEARCH DESIGN AND METHODS— We examined 56 control subjects (aged 51.7 ± 6.4 years) using coronary artery response to the cold pressor test (quantitative coronary angiography) and compared them with 72 type 2 diabetic patients (aged 50.3 ± 8.5 years) without other major coronary risk factors.

RESULTS—Average diameter change was 17.2 ± 10.4% in the control subjects, dilation occurred in 91.1% of subjects, no change occurred in 8.9%, and there was no constriction. Average diameter change was −14.4 ± 12.1% in diabetic patients (P < 0.001 vs. control subjects), constriction occurred in 73.6%, no change occurred in 26.4%, and there was no dilation. CVEs were recorded with a mean follow-up of 45 ± 19 months. There was 1 CVE in the control group and 26 CVEs in 18 of 72 diabetic patients (P < 0.001 vs. control subjects), with 23 events in 16 of 53 diabetic patients with coronary artery constriction (P < 0.001 vs. control subjects), and 3 events in 2 of 19 diabetic patients with no diameter change (NS vs. control subjects).

CONCLUSIONS—In type 2 diabetic patients without other major coronary risk factors, constriction of angiographically normal coronary arteries to the cold pressor test is predictive of long-term CVEs.