bluuebunny/crossref_metadata_2025 huggingface dataset:
High Incidence of Diabetic Nephropathy in Early-Onset Japanese NIDDM Patients: Risk analysis
Authors: Yokoyama Hiroki , Okudaira Maki , Otani Toshika , Watanabe Chizuru , Takaike Hiroko , Miuira Junnoske , Yamada Hitomi , Mutou Kazuko , Satou Akiko , Uchigata Yasuko , Iwamoto Yasuhiko
Published: March 2007

OBJECTIVE

Because early-onset Japanese NIDDM patients (diagnosed before age 30 years) can develop diabetic end-stage renal failure (ESRF) in their thirties, this study was performed to elucidate the incidence and determinants for the development of diabetic nephropathy.

RESEARCH DESIGN AND METHODS

The incidence of diabetic nephropathy and its relationship to baseline characteristics and long-term metabolic control were determined in 426 early-onset Japanese NIDDM patients who were followed for a mean of 6.8 years.

RESULTS

Of these 426 patients, 41 developed diabetic nephropathy manifested by persistent proteinuria (incidence rate [95%CI]/1,000 person-years; 14.1 [10.4–19.1]). Among patients whose mean HbA1c (measured by a high-performance chromatography method that is standardized and comparable to the one used in the Diabetes Control and Complications Trial study) was around 7% or less, few developed nephropathy. The incidence of nephropathy increased with increasing mean HbA1c level in a dose-dependent manner (χ2 trend = 49.9, P < 0.0001). Diastolic blood pressure and duration of diabetes at entry had significant predictive effects independent of metabolic control.

CONCLUSIONS

The incidence rate of diabetic nephropathy in early-onset Japanese NIDDM patients is potentially high, similar to or higher than that in Pima Indian NIDDM or Caucasian IDDM patients of comparable age. Diabetic nephropathy in NIDDM patients aged in their thirties or forties is likely to be an early feature that leads to ESRF, and this would contribute to the marked increase in the number of new patients with diabetic ESRF in Japan. NIDDM is a serious disease if near-normal glycemia is not achieved.
Use of the Physician Insurers Association of America Database as a Surveillance Tool for Diabetes-Related Malpractice Claims in the U.S.
Authors: Meredith Valerie , Cook Curtiss B , Penman Alan
Published: March 2007

OBJECTIVE

To examine the available national surveillance data on malpractice claims associated with diabetes and to determine the medical specialties having the highest number of claims and the classes and costs of filed claims relating to diabetes.

RESEARCH DESIGN AND METHODS

Data was abstracted from the Data Sharing Reports (DSRs) of the Physicians Insurers Association of America (PIAA), as well as a search of the PIAA's computerized database for the period spanning 1 January 1985 to 31 December 1996. Data on numbers of claims, medical causes of loss, indemnity paid, demographics of claimants and physicians, severity, and medical specialties with diabetes-related claims were available.

RESULTS

A total of 906 diabetes claims were reported to PIAA, and the total indemnity paid was $26,892,848. A significant downward trend (P = 0.004) was noted for the period between 1993 and 1996. Diabetes claimants were older and predominately male, relative to all claimants. Ophthalmology, internal medicine, and general and family practice had the highest rates of reported claims at 16.5, 13.6, and 13.4 diabetes claims per 1,000 claims, respectively. Of the diabetes-related injuries, 44% occurred in the practitioner's office, as compared with 27% for all claims. A greater proportion of diabetes claims were associated with the highest level of severity of injury with respect to all claims compiled by the PIAA.

CONCLUSIONS

The database of the PIAA can be a useful resource to monitor trends in diabetes-related malpractice. Further study into whether claims result from lack of adherence to practice guidelines is needed. Prevention programs designed to reduce the liability among high-risk specialties may also lead to improved care for the patient with diabetes.
Factors Associated With Glycemic Control: A cross-sectional nationwide study in 2,579 French children with type 1 diabetes
Authors: Rosilio Myriam , Cotton Jean-BenoîT , Wieliczko Marie-Claire , Gendrault Bénédicte , Carel Jean-Claude , Couvaras Olga , Ser Nicole , Gillet Pierre , Soskin Sylvie , Garandeau Patrick , Stuckens Chantal , Le Luyer Bernard , Jos Joseph , Bony-Trifunovic Hélène , Bertrand Anne-Marie , Leturcq France , Lafuma Antoine ,   The French Pediatric Diabetes Group, Bougnères Pierre-François
Published: March 2007

OBJECTIVE

To determine on a large scale the multiple medical and nonmedical factors that influence glycemic control in the general population of children with diabetes, we performed a nationwide French cross-sectional study.

RESEARCH DESIGN AND METHODS

We enrolled 2,579 patients aged 1–19 years with type 1 diabetes of > 1 year's duration. The study was center based: 270 centers were identified, 206 agreed to participate, and 147 included at least 90% of their patients. Questionnaires were completed by physicians interviewing patients and family, and HbA1c measurements were centralized. To identify explanatory variables for HbA1c level and frequency of severe hypoglycemia, we performed multiple regression analysis using all the quantitative variables collected and stepwise logistic regression for the qualitative variables.

RESULTS

Mean HbA1c value for the whole population was 8.97 ± 1.98% (normal 4.7 ± 0.7% [SD]). Only 19 children (0.7%) had ketoacidosis during the 6 months before the study, whereas 593 severe hypoglycemia events occurred in 338 children (13.8%). Control was better in university-affiliated hospitals and centers following > 50 patients, reflecting the importance of access to experienced diabetologists. Children had a mean of 2.3 injections, allegedly performed 2.8 glucose measurements per day, and were seen an average of 4.6 times per year at the center. In the multiple regression analysis, 94% of the variance of HbA1c was explained by our pool of selected variables, with the highest regression coefficient between HbA1c and age (Rc = 0.43, P < 0.0001), then with daily insulin dosage per kilogram (Rc = 0.28, P < 0.0001), mother's age (Rc = 0.26, P < 0.0001), frequency of glucose measurements (Rc = 0.21, P < 0.0001), and diabetes duration (Rc = 0.14, P < 0.0001). Logistic regression identified quality of family support and dietary compliance, two related qualitative and possibly subjective variables, as additional explanatory determinants of HbA1c. The frequency of severe hypoglycemia was 45 per 100 patient-years and correlated with diabetes duration, but not with HbA1c levels or other variables.

CONCLUSIONS

Although overall results remain unsatisfactory, 33% of studied French children with type 1 diabetes had HbA1c <8%, the value obtained in Diabetes Control and Complications Trial adolescents treated intensively. Diabetes management in specialized centers should be encouraged.
Effects of Diabetes and Level of Glycemia on All-Cause and Cardiovascular Mortality: The San Antonio Heart Study
Authors: Wei Ming , Gaskill Sharon P , Haffner Steven M , Stern Michael P
Published: March 2007

OBJECTIVE

Although the level of hyperglycemia is clearly a risk factor for microvascular complications in diabetic patients, its role in macrovascular complications remains controversial. We followed 4,875 subjects (65% Mexican-American) for 7–8 years to investigate the effects of diabetes and hyperglycemia on all-cause and cardiovascular disease (CVD) mortality. These end points were also analyzed according to quartiles of baseline fasting plasma glucose among diabetic participants.

RESEARCH DESIGN AND METHODS

The Cox proportional hazards model was used to estimate the relative risks (RRs) for all-cause and CVD mortality.

RESULTS

Diabetes was significantly associated with increased all-cause mortality (RR [95% CI] = 2.1 [1.3–3.5] in men; 3.2 [1.9–5.4] in women) and increased CVD mortality (3.2 [1.4–7.1] in men; 8.5 [2.8–25.2] in women). Among diabetic subjects, those in quartile 4 had a 4.2-fold greater risk of all-cause mortality (P < 0.001) and a 4.7-fold greater risk of CVD mortality (P = 0.01) than those in quartiles 1 and 2 combined. After further adjustment for other potential risk factors, subjects in quartile 4 had a 4.9-fold greater risk of all-cause mortality and a 4.9-fold greater risk of CVD mortality than those in quartiles 1 and 2. In addition, hypertension, current smoking, and cholesterol >6.2 mmol/1 were significant predictors of CVD mortality using Cox models.

CONCLUSIONS

We conclude that diabetes is a predictor of both all-cause and CVD mortality in the general population and that both hyperglycemia and common CVD risk factors are important predictors of all-cause and CVD mortality in diabetic subjects.
Hyperinsulinemia and Carotid Atherosclerosis in Hypertensive and Control Subjects
Authors: Rantala Asko O , Päivänsalo Markku , Kauma Heikki , Lilja Mauno , Savolainen Markku J , Reunanen Antti , Kesäniemi Y Antero
Published: March 2007

OBJECTIVE

To analyze the relationships between carotid atherosclerosis measured as intima-media thickness (IMT) and different measures of insulin in a population-based casecontrol study of men and women.

RESEARCH DESIGN AND METHODS

Carotid ultrasonographic measurements and 2-h oral glucose tolerance tests were performed in a random sample of 513 hypertensive subjects, aged 40–59 years, and in 518 age- and sex-matched control subjects. The associations between IMT and the different measures of insulin were analyzed through multiple regression and by insulin quintiles. The independent effect of insulin was estimated after concurrent adjustment for age, obesity, LDL cholesterol, and systolic blood pressure.

RESULTS

The most powerful correlates with IMT were LDL cholesterol, age, systolic blood pressure, pack-years of smoking, and of the different insulin parameters, 2-h post-load insulin. In stepwise regression analysis, the independent predictors of the mean IMT were LDL cholesterol, systolic blood pressure, pack-years of smoking, and age (P < 0.0001) after adjustment for the independent predictors. In analysis of variance, no positive association of insulin parameters with IMT was found between the 2-h insulin quintiles after adjustment for the independent variables. The exclusion of diabetic subjects did not change the results.

CONCLUSIONS

The present study of a population-based sample of men and women found inconsistent associations between different insulin measures and IMT after adjustment for the independent variables.
Combined Use of a Fasting Plasma Glucose Concentration and HbA1c or Fructosamine Predicts the Likelihood of Having Diabetes in High-Risk Subjects
Authors: Ko Gary T C , Chan Juliana C N , Yeung Vincent T F , Chow Chun-Chung , Tsang Lynn W W , Li June K Y , So Wing-Yi , Wai Hendena P S , Cockram Clive S
Published: March 2007

OBJECTIVE

To assess the validity of using fasting plasma glucose (FPG) concentrations in conjunction with HbA1c or fructosamine for the screening of diabetes in high-risk individuals.

RESEARCH DESIGN AND METHODS

In this study 2,877 Hong Kong Chinese (565 [19.6%] men; 2,312 [80.4%] women) with various risk factors for glucose intolerance underwent a 75-g oral glucose tolerance test (OGTT) for screening of diabetes. The risk factors included a family history positive for diabetes, a history of gestational diabetes or impaired glucose tolerance, and obesity.

RESULTS

Using World Health Organization (WHO) criteria, 1,593 (55.4%) had normal glucose tolerance, 657 (22.8%) had impaired glucose tolerance, and 627 (21.8%) had diabetes. When the 1997 American Diabetes Association (ADA) criteria were applied, 394 (13.7%) had diabetes with an FPG ≥ 7.0 mmol/l. Using multiple receiver operating characteristic curve analysis, the paired values of an FPG of 5.6 mmol/l and a HbA1c of 5.5% gave an optimal sensitivity of 83.8% and specificity of 83.6% to predict a 2-h plasma glucose (PG) ≥ 11.1 mmol/l. Likewise, the paired values of an FPG of 5.4 mmol/l and a fructosamine level of 235 mumol/l (n = 2,408) gave an optimal sensitivity of 81.5% and specificity of 83.2%. An FPG ≥ 5.6 mmol/l and an HbA1c ≥ 5.5% was 5.4-fold more likely to occur in diabetic subjects (based on the WHO criteria) compared with nondiabetic subjects. For paired parameters less than these values, the likelihood ratio of this occurring in diabetic subjects was only 0.11. Similarly, an FPG ≥ 5.4 mmol/l and a fructosamine ≥ 235 μmol/l was fivefold more likely to occur in diabetic subjects than in nondiabetic subjects, with both parameters less than these values having a likelihood ratio of 0.04. Using these paired values as initial screening tests, only subjects who had an FPG ≥ 5.6 mmol/l and < 7.8 mmol/l and a fructosamine ≥235 μmol/1 (n = 526) required OGTT to confirm diabetes, meaning that 78.2% [(2,408 – 526)/2,408] of the OGTTs could have been saved. Based on the 1997 ADA criterion of an FPG cutoff value of 7.0 mmol/1, the corresponding numbers of OGTTs to be saved were 82.6% and 85.5%, respectively.

CONCLUSIONS

The paired values of FPG and HbA1c or FPG and fructosamine helped to identify potentially diabetic subjects, the diagnosis of which could be further confirmed by the 75-g OGTT. Using this approach ∼ 80% of OGTTs could have been saved, depending on the diagnostic cutoff value of FPG.
Is the Risk of Diabetic Retinopathy Greater in Non-Hispanic Blacks and Mexican Americans Than in Non-Hispanic Whites With Type 2 Diabetes?: A U.S. population study
Authors: Harris Maureen I , Klein Ronald , Cowie Catherine C , Rowland Michael , Byrd-Holt Danita D
Published: March 2007

OBJECTIVE

To compare the risk for diabetic retinopathy in non-Hispanic white, non-Hispanic black, and Mexican-American adults with type 2 diabetes in the U.S. population.

RESEARCH DESIGN AND METHODS

Representative population-based samples of people aged ≥ 40 years in each of the three racial/ethnic groups were studied in the 1988–1994. Third National Health and Nutrition Examination Survey (NHANES III). Diagnosed diabetes was ascertained by medical history interview, and undiagnosed diabetes by measurement of fasting plasma glucose. A fundus photograph of a single eye was taken with a nonmydriatic camera, and a standardized protocol was used to grade diabetic retinopathy. Information on risk factors for retinopathy was obtained by interview and standard laboratory procedures.

RESULTS

Prevalence of any lesions of diabetic retinopathy in people with diagnosed diabetes was 46% higher in non-Hispanic blacks and 84% higher in Mexican Americans, compared with non-Hispanic whites. Blacks and Mexican Americans also had higher rates of moderate and severe retinopathy and higher levels of many putative risk factors for retinopathy. Blacks had lower retinopathy prevalence among those with undiagnosed diabetes. In logistic regression, retinopathy in people with diagnosed diabetes was associated only with measures of diabetes severity (duration of diabetes, HbA1c, level, treatment with insulin and oral agents) and systolic blood pressure. After adjustment for these factors, the risk of retinopathy in Mexican Americans was twice that of non-Hispanic whites, but non-Hispanic blacks were not at higher risk for retinopathy. These risks were similar when people with undiagnosed diabetes were included in the logistic regression models.

CONCLUSIONS

The prevalence and severity of diabetic retinopathy is greater in non-Hispanic blacks and Mexican Americans with type 2 diabetes in the U.S. population than in non-Hispanic whites. For blacks, this can be attributed to their higher levels of risk factors for retinopathy, but the excess risk in Mexican Americans is unexplained.
Adverse Effects of Diabetes on Multiple Cardiovascular Disease Risk Factors in Women: The Strong Heart Study
Authors: Howard Barbara V , Cowan Linda D , Go Oscar , Welty Thomas K , Robbins David C , Lee Elisa T ,   Strong Heart Study Investigators
Published: March 2007

OBJECTIVE

Many studies have shown that diabetes increases the risk of cardiovascular disease (CVD) in women to a greater extent than in men. One explanation could be that diabetes has more adverse effects on CVD risk factors in women than in men. We compared diabetes-associated differences in CVD risk factors in men and women in the Strong Heart Study, a population-based study of CVD and its risk factors in American Indians.

RESEARCH DESIGN AND METHODS

A total of 1,846 men and 2,703 women between the ages of 45 and 74 years from 13 American Indian communities in three geographic areas underwent an examination that included a medical history; an electrocardiogram; anthropometric and blood pressure measurements; an oral glucose tolerance test; and measurements of fasting plasma lipoproteins, fibrinogen, insulin, HbA1c, and urinary albumin.

RESULTS

Statistically significantly greater adverse differences in those with diabetes versus those without diabetes were observed in women than in men for waist-to-hip ratio, HDL cholesterol, apolipoprotein (apo)B, apoA1, fibrinogen, and LDL size. In multiple linear regression models adjusting for age, center, sex, and diabetes, the diabetes by sex interaction terms were statistically significant for waist-to-hip ratio, LDL cholesterol, HDL cholesterol, apoB, apoA1, fibrinogen, and LDL size.

CONCLUSIONS

Compared with diabetes-associated differences in men, diabetes in women was related to greater adverse differences in levels of several CVD risk factors. Although the magnitude of the individual diabetes-related differences between men and women was not large, the combined effects of these risk factor differences in diabetic women may be substantial. The apparent greater negative impact of diabetes on CVD risk factors in women may explain, in part, the greater risk for CVD in diabetic women.
Was There an Epidemic of Diabetes in Nonwhite Adolescents in Allegheny County, Pennsylvania?
Authors: Libman Ingrid M , LaPorte Ronald E , Becker Dorothy , Dorman Janice S , Drash Allan L , Kuller Lewis
Published: March 2007

OBJECTIVE

To determine the incidence of IDDM in children aged < 20 years at diagnosis in Allegheny County, Pennsylvania, for the period from 1 January 1990 to 31 December 1994 and to compare the incidence between whites and nonwhites in the same area and for the same time period.

RESEARCH DESIGN AND METHODS

All new patients diagnosed between January 1990 and December 1994 who were aged < 20 years, on insulin, and residents of Allegheny County at diagnosis were identified from medical records of 23 hospitals in the Allegheny County area. To verify the completeness of the hospitals using the capture-recapture method, pediatricians and diabetologists were used as a secondary source.

RESULTS

A total number of 257 patients were identified. The overall age-standardized incidence rate was 16.7/100,000. Nonwhites had a slightly higher incidence (17.6/100,000) than whites (16.5/100,000). In the 15–19 years age-group, the incidence in nonwhites (30.4/100,000) was almost three times higher than that in white (11.2/100,000) and more than two times higher than that in the previous period (from 1985 to 1989) (13.8/100,000).

CONCLUSIONS

For the first time in the Allegheny County registry, and in any other registry, nonwhites showed a higher incidence of IDDM than whites. The high incidence in the 15–19 years age-group was responsible for this phenomenon. This epidemic of diabetes in adolescent nonwhites may be the result of a rising incidence of classical IDDM or another type of diabetes. Further studies using population-based registries are needed to determine whether this increase is being seen in other areas and other ethnic groups and to clarify the reasons for the increase in IDDM among blacks.
Further Evidence for a Central Role of Adipose Tissue in the Antihyperglycemic Effect of Metformin
Authors: Abbasi Fahim , Carantoni Marcello , Chen Y -D I , Reaven Gerald M
Published: March 2007

OBJECTIVE

To evaluate further the relative roles played by liver and adipose tissue in the therapeutic response to metformin in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS

A total of 11 patients with diet-treated type 2 diabetes were given metformin for ∼ 3 months. Measurements were made before and after treatment of 1) fasting and postprandial plasma glucose, insulin, and free fatty acid (FFA) concentrations; 2) glucose appearance (Ra) and disappearance (Rd) rates measured overnight with 3-[3H]glucose; and 3) plasma FFA concentrations during a 195-min infusion period at relatively low insulin (∼ 12–24 μU/ml) concentrations.

RESULTS

Mean ± SEM fasting plasma glucose concentration was significantly lower (175 ± 11 vs. 224 ± 15 mg/dl; P < 0.01) after treatment with metformin. Mean ± SEM insulin concentrations measured from 8:00 A.M. to 5:00 P.M. did not change with treatment. However, both glucose and FFA concentrations were significantly lower (P < 0.01) when measured over the same time period, and the decreases in plasma FFA and glucose concentration were highly correlated (r = 0.81; P = 0.03). Overnight glucose turnover studies indicated that neither Ra (hepatic glucose production [HGP]) nor Rd changed significantly with treatment in association with metformin treatment. Since plasma glucose concentration was much lower after metformin treatment, the overnight glucose metabolic clearance rate (MCR) was significantly lower (P < 0.01). Finally, the ability of insulin to inhibit isoproterenol-stimulated increases in plasma FFA concentration was enhanced in metformin-treated patients (P < 0.05).

CONCLUSIONS

Metformin treatment was associated with significantly lower fasting plasma glucose concentrations and lower day-long plasma glucose and FFA concentrations. Although overnight HGP was unchanged after treatment with metformin, the overnight glucose MCR was significantly increased, and the antilipolytic activity of insulin was also enhanced. Given these findings, it is suggested that at least part of the antihyperglycemic effect of metformin is due to a decrease in release of FFA from adipose tissue, leading to lower circulating FFA concentrations and an increase in glucose uptake.
Diabetic Nephropathy in Hypertransfused Patients With β-Thalassemia: The role of oxidative stress
Authors: Loebstein Ronen , Lehotay Denis C , Luo Xiaoping , Bartfay Wally , Tyler Bev , Sher Graham D
Published: March 2007

OBJECTIVE

Pathogenesis of diabetes-related microvascular complications involving oxidative damage by free radicals has been demonstrated. Free radical generation has been shown to derive largely from iron. Our objectives, therefore, were to determine if there is an increased incidence and/or an accelerated course of nephropathy in patients with diabetes, secondary to transfusional hemochromatosis, and to examine whether free radical activity contributes to the development of this complication.

RESEARCH DESIGN AND METHODS

We evaluated nine patients with homozygous β-thalassemia, complicated by clinically overt diabetes, for diabetic nephropathy over a 7-year period. Lipid peroxidation was quantified by measuring the presence of 20 saturated and unsaturated aldehydes, and results were compared with five normotensive type 1 diabetic patients without iron overload.

RESULTS

Nephropathy developed in five of nine patients (55%) after a mean duration of overt diabetes of 3.6 ± 2.0 years. Three patients showed evidence of progressive microalbuminuria over a 7-year period (24.7–46.2, 52.2–430.1, and 17.7–54.3 μg/min, respectively). Two patients with borderline microalbuminuria (19.9 and 14.5 μg/min, respectively) demonstrated stable albumin excretion rates over the follow-up period. Total aldehyde concentration was significantly higher in β-thalassemia diabetic patients, compared with nonthalassemic diabetic control subjects (8,106 ± 1,280 vs. 4,594 ± 247 nmol/l; P < 0.0001). The three patients with progressive microalbuminuria demonstrated significantly higher total aldehyde concentration, compared with the other β-thalassemia diabetic patients with stable albumin excretion (9,428 ± 337 vs. 7,445 ± 1,003 nmol/l; P < 0.01). Serum vitamin E concentrations were significantly lower in β-thalassemia patients with diabetes, compared with diabetic patients without iron overload (12.1 ± 6.0 vs. 25.9 ± 11.4 μ/l; P = 0.02). Serum vitamin C concentrations did not differ between the two groups. Multiple regression analysis demonstrated total aldehyde concentration to be the most significant predictor for the development of microalbuminuria (P = 0.01), followed by the duration of diabetes (P = 0.02) and glycemic control (P = 0.02).

CONCLUSIONS

Early development and an accelerated course of diabetic nephropathy in iron-loaded patients with β-thalassemia are observed. These findings may be attributed to high oxidative stress in these patients, which is secondary to iron-derived free radicals and to the patients' diminished antioxidant reserves.
Physiological Importance of First-Phase Insulin Release in Elderly Patients With Diabetes
Authors: Meneilly Graydon S , Elahi Dariush
Published: March 2007

OBJECTIVE

To assess the physiological role of first-phase insulin release in obese elderly patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS

Moderately obese elderly patients (n = 14, mean age 77 ± 2 years, BMI 28.4 ± 0.7 kg/m2) with type 2 diabetes underwent three 180-min hyperglycemic clamp studies. In the control study, glucose alone was infused. In the first-phase study, human insulin was infused for the first 4 min at 12 mU/m2 to mimic first-phase insulin release. In the first-phase enhanced study, insulin was infused for the first 4 min at 24 mU · m−2 · min−1. Tritiated glucose methodology was used in all studies to measure glucose production and disposal rates.

RESULTS

Glucose values were similar in all studies. In the control study, first-phase insulin response was absent. The peak insulin response occurred at 4 min in the first-phase and first-phase enhanced studies, but insulin values were substantially higher in the latter study (528 ± 40 vs. 340 ± 24 pmol/l, P < 0.0001). Second-phase insulin responses were not different among the studies. Glucose production and disposal rates were not significantly different among the studies.

CONCLUSIONS

While absent first-phase insulin secretion is a marker of abnormal pancreatic function in obese elderly patients with type 2 diabetes, it is not important in the regulation of hepatic glucose output or peripheral glucose disposal.
Differences in Foot and Forearm Skin Microcirculation in Diabetic Patients With and Without Neuropathy
Authors: Arora Subodh , Smakowski Paula , Frykberg Robert G , Simeone Louis R , Freeman Roy , LoGerfo Frank W , Veves Aristidis
Published: March 2007

OBJECTIVE

We have compared the hyperemic response to heat and the endothelium-dependent and endothelium-independent vasodilatation between the dorsum of the foot and the forearm in diabetic neuropathic and non-neuropathic patients and healthy control subjects.

RESEARCH DESIGN AND METHODS

We studied the cutaneous microcirculation in the forearm and foot in 15 diabetic patients with neuropathy, in 14 diabetic patients without neuropathy, and in 15 control subjects matched for age, sex, BMI, and in the case of diabetic patients, for the duration of diabetes. Patients with peripheral vascular disease and/or renal impairment were excluded. The cutaneous microcirculation of the dorsum of the foot and the flexor aspect of the forearm was tested in all subjects. Single-point laser Doppler was employed to measure the maximal hyperemic response to heating of the skin to 44°C and laser Doppler imaging scanner was used to evaluate the response to iontophoresis of 1% acetylcholine chloride (Ach) (endothelium-dependent response) and 1% sodium nitroprusside (NaNP) (endothelium-independent response).

RESULTS

The transcutaneous oxygen tension was lower in the neuropathic group at both foot and forearm level, while the maximal hyperemic response to heat was similar at the foot and forearm level in all three groups. The endothelium-dependent vasodilation (percent increase over baseline) was lower in the foot compared to the forearm in the neuropathic group (23 ± 4 vs. 55 ± 10 [mean ± SEM] P < 0.01)], the non-neuropathic group (33 ± 6 vs. 88 ± 14; P < 0.01), and the control subjects (43 ± 6 vs. 93 ± 13; P < 0.001). Similar results were observed during the iontophoresis of NaNP (P < 0.05). No differences were found among the three groups when the ratio of the forearm:foot response was calculated for both the endothelium-dependent (neuropathic group, 2.25 ± 0.24; non-neuropathic group, 2.55 ± 0.35; and control subjects, 2.11 ± 0.26; P = NS) and endothelium-independent vasodilation (neuropathic group, 1.54 ± 0.27; non-neuropathic group, 2.08 ± 0.33; and control subjects, 2.77 ± 1.03; P = NS). The vasodilatory response, which is related to the C nociceptive fiber action, was reduced at the foot level during iontophoresis of Ach in the neuropathic group. In contrast, no difference was found during the iontophoresis of NaNP at the foot and forearm level and of Ach at the forearm level among all three groups.

CONCLUSIONS

In healthy subjects, the endothelial-dependent and endothelial-independent vasodilatation is lower at the foot level when compared to the forearm, and a generalized impairment of the microcirculation in diabetic patients with neuropathy preserves this forearm-foot gradient. These changes may be a contributing factor for the early involvement of the foot with neuropathy when compared to the forearm.
Attitudes of Primary Care Providers Toward Diabetes: Barriers to guideline implementation
Authors: Larme Anne C , Pugh Jacqueline A
Published: March 2007

OBJECTIVE

Primary care providers have been slow to adopt standards of care for diabetes, and continuing medical education (CME) programs have been minimally effective in changing provider behavior. The objective of this study was to explore the previously reported finding that attitudes, rather than knowledge, may impede primary care provider adherence to standards of care.

RESEARCH DESIGN AND METHODS

Study participants included 31 primary care providers attending an eight-session CME program on diabetes. Providers rated on a 10-point scale how the treatment of diabetes compared with that of five other chronic conditions (hypertension, hyperlipidemia, angina, arthritis, and heart failure; 1 = easier to 10 = harder; midpoint 5.5). In a subsequent open-ended qualitative interview, providers explained their scale ratings.

RESULTS

Diabetes was rated as significantly harder to treat than hypertension (24 of 30 >5.5; P < 0.001) and angina (20 of 30 >5.5; P = 0.03). A majority also rated hyperlipidemia (18 of 30) and arthritis (18 of 30) as easier to treat than diabetes. Explanatory themes underlying provider frustrations with diabetes include characteristics of the disease itself and the complexity of its management, and a perceived lack of support from society and the health care system for their efforts to control diabetes.

CONCLUSIONS

CME that addresses provider attitudes toward diabetes in addition to updating knowledge may be more effective than traditional CME in promoting adherence to standards of care. Additional changes are needed in our health care system to shift from an acute to a chronic disease model to effectively support diabetes care efforts.
Accuracy of Calculated Serum Low-Density Lipoprotein Cholesterol for the Assessment of Coronary Heart Disease Risk in NIDDM Patients
Authors: Branchi Adriana , Rovellini Angelo , Torri Adriana , Sommariva Domenico
Published: March 2007

OBJECTIVE

To evaluate the accuracy of LDL cholesterol calculated with Friedewald's equation in the assessment of cardiovascular risk in NIDDM patients.

RESEARCH DESIGN AND METHODS

The calculation of LDL cholesterol according to Friedewald's formula was compared with the measurement of LDL cholesterol separated by ultracentrifugation in 151 NIDDM patients with fairly good metabolic control (HbA1c ≤10%) and in 405 nondiabetic subjects.

RESULTS

Measured and calculated LDL cholesterol was found to be well correlated in both diabetic (r = 0.95) and nondiabetic (r = 0.97) subjects. Compared with measured LDL cholesterol, the calculated LDL cholesterol differed by ≥10% in 34% of samples from diabetic patients and in 26% of samples from nondiabetic subjects (χ2 = 3.885, P < 0.05). The percentage of error increased when the serum triglyceride (TG) level was ≥200 mg/dl (2.26 mmol/l) and when the ratio of VLDL cholesterol to TG was <0.20 or >0.29 in both groups of subjects. Although the percentage of error from calculated LDL cholesterol was greater in diabetic than in nondiabetic subjects because of the greater prevalence of hypertriglyceridemia in the former group, the misclassification of coronary heart disease risk, according to the cutoff points of the National Cholesterol Education Program (NCEP), was similar in the two groups (25% in diabetic and 22% in nondiabetic subjects). In both groups of patients, the misclassification of coronary heart disease risk was higher when calculation of LDL cholesterol produced values near the cutoff points.

CONCLUSIONS

Although accuracy in the estimation of LDL cholesterol is less than ideal, Friedewald's equation seems to be of value in the correct assignment of coronary heart disease risk classes in the great majority of diabetic as well as nondiabetic subjects. Caution must be exercised for subjects in whom calculated LDL cholesterol is close to the cutoff points of the NCEP guidelines.
Troglitazone in Combination With Sulfonylurea Restores Glycemic Control in Patients With Type 2 Diabetes
Authors: Horton Edward S , Whitehouse Fred , Ghazzi Mahmoud N , Venable Tom C ,   The Troglitazone Study Group, Whitcomb Randall W
Published: March 2007

OBJECTIVE

To determine if the combination of troglitazone (a peroxisome proliferator-activated receptor-γ activator) and sulfonylurea will provide efficacy not attainable by either medication alone.

RESEARCH DESIGN AND METHODS

There were 552 patients inadequately controlled on maximum doses of sulfonylurea who participated in a 52-week randomized active-controlled multicenter study. Patients were randomized to micronized glyburide 12 mg q.d. (G12); troglitazone monotherapy 200, 400, or 600 mg q.d. (T200, T400, T600); or combined troglitazone and glyburide q.d. (T200/G12, T400/G12, T600/G12). Efficacy measures included HbA1c, fasting serum glucose (FSG), insulin, and C-peptide. Effects on lipids and safety were also assessed.

RESULTS

Patients on T600/G12 had significantly lower mean (± SEM) FSG (9.3 ± 0.4 mmol/l; 167.4 ± 6.6 mg/dl) compared with control subjects (13.7 ± 0.4 mmol/l; 246.5 ± 6.8 mg/dl; P < 0.0001) and significantly lower mean HbA1c (7.79 ± 0.2 vs. 10.58 ± 0.18%, P < 0.0001). Significant dose-related decreases were also seen with T200/G12 and T400/G12. Among patients on T600/G12, 60% achieved HbA1c ≤8%, 42% achieved HbA1c ≤7%, and 40% achieved FSG ≤7.8 mmol/l (140 mg/dl). Fasting insulin and C-peptide decreased with all treatments. Overall, triglycerides and free fatty acids decreased, whereas HDL cholesterol increased. LDL cholesterol increased slightly, with no change in apolipoprotein B. Adverse events were similar across treatments. Hypoglycemia occurred in 3% of T600/G 12 patients compared with <1% on G12 or troglitazone monotherapy

CONCLUSIONS

Patients with type 2 diabetes inadequately controlled on sulfonylurea can be effectively managed with a combination of troglitazone and sulfonylurea that is safe, well tolerated, and represents a new approach to achieving the glycemic targets recommended by the American Diabetes Association.
Biologic Material in Needles and Cartridges After Insulin Injection With a Pen in Diabetic Patients
Authors: Le Floch Jean-Pierre , Herbreteau Catherine , Lange Françoise , Perlemuter Léon
Published: March 2007

OBJECTIVE

To evaluate the frequency of non-inert material, including cells, in needles and cartridges after insulin injection with pen-like devices in diabetic patients.

RESEARCH DESIGN AND METHODS

A prospective study was conducted in 120 insulin-treated diabetic patients who used pen-like devices. The patients, 46 women and 74 men, were 20–77 years old; 60% had type 1 diabetes, and 38% were overweight. Duration of diabetes ranged from 1 month to 40 years, and insulin therapy ranged from 1 month to 30 years. Insulin injection was performed by a trained nurse, using the patient's usual pen and cartridge. A cytopathological examination was performed on the material obtained from the needle and found in the cartridge after centrifugation. All slides were read by a single investigator.

RESULTS

In 62% of the patients, non-inert material was found, including squamous (32%) and epithelial (58%) cells. Biologic material was found in 30% of the needles and 58% of the cartridges, and in both needle and cartridge in 25% of the population. Biologic material was found more frequently in patients who had a longer duration of diabetes, who were treated with insulin for a longer time, and who performed injection in the thighs or upper arms (P < 0.05). In multivariate analysis, the presence of biologic material was associated with the duration of diabetes (R2 = 0.09; P < 0.01).

CONCLUSIONS

Our data suggest that biologic material can be trapped in the delivery system, including the cartridge, after an insulin injection with a pen-like device. Our results emphasize the strict need for individual use of insulin delivery systems, including cartridges and nonrefillable pens, especially in clinics and hospitals.
Improved glycemic control and lipid profile and normalized fibrinolytic activity on a low-glycemic index diet in type 2 diabetic patients.
Authors: Järvi A E , Karlström B E , Granfeldt Y E , Björck I E , Asp N G , Vessby B O
Published: March 2007

OBJECTIVE: To evaluate the effects of varying the glycemic index (GI) of carbohydrate-rich foods on metabolic control in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: In a randomized crossover study, 20 patients, 5 women and 15 men, were given preweighed diets with different GIs during two consecutive 24-day periods. Both diets were composed in accordance with dietary recommendations for people with diabetes. The macronutrient composition and type and amount of dietary fiber were identical. Differences in GI were achieved mainly by altering the structure of the starchy foods. RESULTS: Peripheral insulin sensitivity increased significantly and fasting plasma glucose decreased during both treatment periods. There was a significant difference in the changes of serum fructosamine concentrations between the diets (P < 0.05). The incremental area under the curve for both blood glucose and plasma insulin was approximately 30% lower after the low- than after the high-GI diet. LDL cholesterol was significantly lowered on both diets, with a significantly more pronounced reduction on the low-GI diet. Plasminogen activator inhibitor-1 activity was normalized on the low-GI diet, (-54%, P < 0.001), but remained unchanged on the high-GI diet. CONCLUSIONS: A diet characterized by low-GI starchy foods lowers the glucose and insulin responses throughout the day and improves the lipid profile and capacity for fibrinolysis, suggesting a therapeutic potential in diabetes.
Elevated remnant-like lipoprotein particles in impaired glucose tolerance and type 2 diabetic patients.
Authors: Watanabe N , Taniguchi T , Taketoh H , Kitagawa Y , Namura H , Yoneda N , Kurimoto Y , Yamada S , Ishikawa Y
Published: March 2007

OBJECTIVE: Impaired glucose tolerance (IGT) in association with insulin resistance is considered to be a risk factor for atherosclerosis. Thus, patients with IGT may have abnormal lipid and lipoprotein profiles. The purpose of this study was to investigate presence of remnant-type hyperlipoproteinemia in patients with IGT. RESEARCH DESIGN AND METHODS: Serum levels of remnant-like lipoprotein particles (RLP) were measured in 541 subjects (362 men and 179 women, age 53 +/- 7.9 years) who visited our health center for routine medical examinations. We measured RLP cholesterol (RLP-C) and RLP triglycerides (RLP-TG) using immunoaffinity gel containing monoclonal anti-human apoproteins A-I (H-12) and B-100 (JI-H) antibodies. After a 75-g oral glucose tolerance test, subjects were divided into three groups: normal, IGT, and type 2 diabetic. RESULTS: After matching for sex, age, and body weight, serum RLP-C in normal, IGT, and diabetic groups were 4.2 +/- 1.7, 6.2 +/- 3.4, and 6.2 +/- 4.2 mg/dl, respectively. The corresponding RLP-TG values were 16.7 +/- 9.2, 28.0 +/- 19.1, and 29.0 +/- 27.2 mg/dl. We found that RLP-C and RLP-TG values were significantly higher in the IGT and diabetic groups compared with the normal group (P < 0.001). In the same order, total serum cholesterol levels were 206 +/- 29, 205 +/- 34, and 206 +/- 34 mg/dl and LDL cholesterol levels were 127 +/- 27, 124 +/- 34, and 123 +/- 34 mg/dl, showing no marked difference in these groups. However, serum levels of triglyceride were higher in the IGT and diabetes groups (155 +/- 76 and 151 +/- 81 mg/dl vs. 106 +/- 41 mg/dl; P < 0.0001). Further, the incidence of remnant hyperlipoproteinemia in normocholesterolemic subjects was up to four times higher in IGT and diabetic groups compared with the normal group. CONCLUSIONS: High serum RLP-C and RLP-TG levels in IGT and diabetic patients may represent an increased risk of atherosclerosis in these patients.
Prediction of cardiovascular events in clinically selected high-risk NIDDM patients. Prognostic value of exercise stress test and thallium-201 single-photon emission computed tomography.
Authors: Vanzetto G , Halimi S , Hammoud T , Fagret D , Benhamou P Y , Cordonnier D , Denis B , Machecourt J
Published: March 2007

OBJECTIVE: We evaluated the prognostic value of an exercise stress test and thallium-201 scintigraphy for the prediction of cardiac events in selected high-risk NIDDM patients. RESEARCH DESIGN AND METHODS: NIDDM patients (n = 158, 105 men, aged 63 +/- 9 years) with two or more of the following criteria were prospectively included: age > or = 65 years, active smoking, hypertension > 160/95 mmHg, hypercholesterolemia (cholesterol > 5.70 mmol/l or LDL > 3.10 mmol/l), peripheral artery disease, abnormal rest electrocardiogram, or microalbuminuria (20-200 micrograms/min). An exercise-stress scintigraphy was performed in 77 patients able to exercise, while a dipyridamole scintigraphy was performed in 80 patients unable to exercise. Follow-up was 23 +/- 17 months. Major end points were cardiac deaths or nonfatal myocardial infarction. RESULTS: The annual event rate was 7.31% (deaths: 8, myocardial infarction: 14). Independent predictors of events were as follows: an age > 60 (P = 0.02), an abnormal rest electrocardiogram (P = 0.02), microalbuminuria (P = 0.001), the inability to exercise (P = 0.009), and the presence of more than two defects on scintigraphy (P = 0.001). A cardiac death occurred in 1.3% of patients able to exercise versus 8.8% of patients unable to exercise (odds ratio = 6.8, P = 0.001). Among patients unable to exercise, large perfusion defects corresponded to an annual mortality rate of 22.3%. Conversely, the negative predictive value of a normal scintigraphy for the occurrence of death was 97%. CONCLUSIONS: Inability to exercise and large perfusion defects on thallium-201 scan are major predictors of future death and myocardial infarction in high-risk NIDDM patients.
Lispro or regular insulin for multiple injection therapy in adolescence. Differences in free insulin and glucose levels overnight.
Authors: Mohn A , Matyka K A , Harris D A , Ross K M , Edge J A , Dunger D B
Published: March 2007

OBJECTIVE: Regular insulin given with the evening meal could contribute to the risk of nocturnal hypoglycemia in adolescents with type 1 diabetes using a multiple injection regimen. To test this hypothesis, we compared glucodynamics and free insulin levels on two separate study nights. RESEARCH DESIGN AND METHODS: A total of 14 adolescents were recruited. On both nights, identical doses of regular insulin or insulin lispro were administered 30 min or 10 min, respectively, before the evening meal, using a double-blind randomized crossover study design. Doses of NPH insulin and carbohydrate content of the evening meal and snack were kept identical. Blood samples were taken every 15 min for blood glucose and every 60 min for free insulin and ketones. RESULTS: After insulin lispro administration, glucose levels were significantly lower between the evening meal and the bedtime snack (analysis of variance [ANOVA] P = 0.02), and four hypoglycemic episodes were recorded. This corresponded to a higher (458 +/- 48 vs. 305 +/- 33 pmol/l, P = 0.02), earlier (64 +/- 4.6 vs. 103 +/- 12 min, P = 0.01), and shorter-lasting (245 +/- 21 vs. 365 +/- 39 min, P = 0.01) insulin peak in contrast to regular insulin. After the bedtime snack, glucose levels increased dramatically during the lispro night and stayed higher, up to 0300 in the morning (ANOVA P = 0.01), corresponding to lower mean insulin levels (146 +/- 20 vs. 184 +/- 27 pmol/l, P = 0.04). No differences were seen in glucose and insulin levels between 0300 and 0800. Four episodes of nocturnal hypoglycemia were documented after the bedtime snack during the regular insulin night, in contrast to one episode after insulin lispro. No differences in ketone levels were observed. CONCLUSIONS: The replacement of regular insulin with insulin lispro may reduce the risk of late hypoglycemia, but redistribution of the evening carbohydrate may be needed to ensure good metabolic control and prevent early postprandial hypoglycemia.
Social environment and year of birth influence type 1 diabetes risk for African-American and Latino children.
Authors: Lipton R B , Drum M , Li S , Choi H
Published: March 2007

OBJECTIVE: Credible epidemiological data, primarily from European-origin populations, indicate that environmental factors play an important role in the incidence of type 1 diabetes. RESEARCH DESIGN AND METHODS: A population-based registry of incident cases of type 1 diabetes among African-American and Latino children in Chicago was used to explore the influence of individual and neighborhood characteristics on diabetes risk. New cases of insulin-treated diabetes in African-American and Latino Chicagoans aged 0-17 years for 1985-1990 (n = 400) were assigned to one of 77 community areas based on street address. Census tables provided denominators, median household income, percentage of adults > or = 25 years old who had completed high school and college, and a crowding variable for each community area individual-level data were birth cohort, sex, and ethnicity. Outcomes in Poisson regression were sex-, ethnic-, and birth cohort-specific incidence rates. RESULTS: Significant univariate associations between diabetes risk and ethnicity, birth cohort, crowding, and the percentage of adults in each community area who had completed high school and college were observed. African-Americans had a relative risk (RR) of 1.42 (95% CI, 1.14-1.76) compared with Latinos. Risk varied significantly by birth cohort in both ethnic groups. For every 10% increase in the proportion of adults who completed college, the RR for diabetes increased by 25% (RR, 1.25 [95% CI, 1.09-1.44]). Social class variables were significant determinants of risk for African Americans, but not for Latinos. CONCLUSIONS: The strong birth cohort and social class associations observed in this study implicate an infectious exposure linked with age.