bluuebunny/crossref_metadata_2025 huggingface dataset:
Survey of Physician Practice Behaviors Related to Diabetes Mellitus in the U.S.: I. Design and Methods
Authors: Siebert Carolyn , Lipsett Lois F , Greenblatt Janet , Silverman Robert E
Published: March 2007

OBJECTIVE

To conduct a survey among a representative sample of primary care physicians in the U.S. to assess practice behaviors, treatment goals, and beliefs related to management of diabetes mellitus and prevention of its complications.

RESEARCH DESIGN AND METHODS

A mail survey with telephone follow-up was conducted among 3481 primary care physicians in active practice in the continental U.S. A stratified probability sample was selected using the files of the American Medical Association and American Osteopathic Association. Four specialties were selected to be included in the study: family physician, general practitioner, internist, and pediatrician. Two versions of a questionnaire were constructed: one for pediatricians containing questions about IDDM only and one for the other three specialties containing questions about both IDDM and NIDDM. Physicians who were not actively engaged in practice or did not see patients with diabetes were excluded.

RESULTS

Completed questionnaires were received from 1502 of 3481 sampled physicians. Based on various assumptions of eligibility among nonresponders, an overall response rate to the survey was estimated to be between 65.7 and 86.5%. Discrepancies between specialty identifications as noted on the American Medical Association/American Osteopathic Association files and as self-designated were noted.

CONCLUSIONS

This report describes the methodology used in the design and conduct of the survey, and data are provided to document the technical success of survey execution. This report provides the methodological basis for a series of separate reports on demographic characteristics of the physicians, their practices and their patients, and on specific attitudes, beliefs, and practice behaviors of primary care physicians in the U.S. with regard to diabetes mellitus.
Immunogenetic and Clinical Characterization of Slowly Progressive IDDM
Authors: Kobayashi Tetsuro , Tamemoto Koji , Nakanishi Koji , Kato Norihiro , Okubo Minoru , Kajio Hiroshi , Sugimoto Tadao , Murase Toshio , Kosaka Kinori
Published: March 2007

OBJECTIVE

To examine the clinical and immunogenetic heterogeneity of IDDM.

RESEARCH DESIGN AND METHODS

We divided 207 IDDM patients into groups based on the interval from clinical onset to initiation of insulin therapy: group A (<3 mo, acute clinical-onset group, n = 134), group B (3–12 mo, intermediate group, n = 31), and group C (>13 mo, slowly progressive group, n = 42). Immunogenetic and clinical markers were compared between group A and group C.

RESULTS

The mode age of onset was higher in group C (52 yr) than group A (10 yr). Group C had a higher prevalence of islet cell antibodies (42.9%, 18 of 42) than group A (25.4%, 34 of 134, P = 0.05). Serum C-peptide immunoreactivity assayed by radioimmunoassay in response to a 100-g oral glucose tolerance test was significantly higher in group C uhan in group A. Group C patients were also more likely to have a family history of NIDDM (26.1%, 11 of 42) among their first-degree relatives than group A patients (11.2%, 15 of 134, P = 0.039). The prevalences of family history of IDDM and endocrine autoimmune diseases were not different between groups C and A. The frequency of complications of endocrine autoimmune disease was not different between group A (6.7%, 9 of 134) and group C (2.3%, 1 of 42). Significant associations with two class I major histocompatibility complex antigens (HLA-A24 and -Bw54) and one class II antigen (HLA-DR4) were observed in group A. Group A patients were assocciated with three diabetogenic HLA-DQ haplotypes including DQA1*0301-DQB1*0401, DQAl*0301-DQBl*0302, and DQA1 *0301-DQB 1*0303. In contrast, group C lacked the association with class I antigens, although HLA-DR4 and HLA-DQA1* 0301-DQB 1*0401 were more common in this group than in control subjects.

CONCLUSIONS

These results indicate that the clinical subtype with slowly progressive course (slowly progressive IDDM) has distinct findings including late-age onset, high prevalence of islet cell antibodies, preserved β-cell function, and high family history of NIDDM. An additive effect of class I and class II major histocompatibility complex antigens is suggested as an explanation for the acute clinical manifestations and more severe β-cell destruction in group A patients.
Lack of Regional Variation in IDDM Risk in Japan
Authors:   Japan IDDM Epidemiology Study Group
Published: March 2007

OBJECTIVE

To examine the intracountry variation of IDDM incidence in Japan and compare it with data from the British Isles and the U.S.

RESEARCH DESIGN AND METHODS

IDDM incidence was determined with a standardized registry approach in five geographically different areas in Japan (Hokkaido, Tokyo, Yokohama, Osaka, and Kagoshima) with a total at-risk population < 15 yr of age of 4.4 million. Data collection was completed under the guidelines of the World Health Organization Diamond project.

RESULTS

The incidence and patterns of disease were remarkably similar across the five environmentally different areas. Incidence rates per 100,000 were very low and almost identical from northern to southern Japan (Hokkaido, 2.07; Tokyo, 1.65; Yokohama, 1.66; Osaka, 1.78; and Kagoshima, 1.93). This remarkably low intracountry variation of 0.4/100,000 stands in sharp contrast with the 13.0/100,000 regional variation in the British Isles and the 10.6/100,000 variation in the U.S.

CONCLUSIONS

The results suggest that the remarkable genetic homogeneity in Japan may produce uniformity of incidence.
Social and Economic Impact on Youth-Onset Diabetes in Japan
Authors: Matsushima Masato , Tajima Naoko , Agata Toshihiko , Yokoyama Junichi , Ikeda Yoshio , Isogai Yukihide
Published: March 2007

OBJECTIVE

To investigate the social and economic backgrounds of youth-onset insulin-treated diabetes mellitus in Japan.

RESEARCH DESIGN AND METHODS

We conducted a case-control study on 35 diabetic patients with age at onset of 19.5 ±; 5.1 yr and duration of diabetes 14.9 ±; 6.7 yr. Sex- and age-matched (within 5 yr) siblings were selected as control subjects. Thirty-five matched pairs were asked to complete a questionnaire, including employment status and educational achievement.

RESULTS

Overall, diabetic patients were more likely to encounter job refusal in their lives than sibling control subjects (20 vs. 0%), and most patients (6/7) who had an experience of job refusal told job interviewers about their diabetes. Although the full-time employment rate and unemployment rate did not differ significantly between patients and control subjects, income levels were lower among patients than in the sibling (1600 vs. 2500 thousand yen). A multivariate analysis indicated that patients had lower incomes than control subjects after adjusting for the effect of physical disability. Educational achievements in the patients were similar to those in the siblings.

CONCLUSIONS

These results suggested that diabetic patients had several social and economic problems in Japan. Further studies in more subjects are required to grasp the social and economic impact on diabetes precisely, and minimize the social handicaps on diabetic patients.
Effect of Added Fat on Plasma Glucose and Insulin Response to Ingested Potato in Individuals With NIDDM
Authors: Gannon Mary C , Ercan Nacide , Westphal Sydney A , Nuttall Frank Q
Published: March 2007

OBJECTIVE— In normal subjects, ingestion of butter with potato resulted in considerably lower blood glucose levels but similar or higher insulin concentrations compared with those observed in the same subjects after potato ingestion alone. We determined whether butter ingested with potato would result in a greater stimulation in insulin secretion than ingestion of potato alone in subjects with NIDDM.

RESEARCH DESIGN AND METHODS— Seven male subjects with untreated NIDDM ingested 50 g CHO alone or 50 g CHO with 5, 15, 30, or 50 g fat as a breakfast meal. Fat was ingested in the form of butter, and CHO was given in the form of potato. Subjects received 50 g glucose on two separate occasions for comparative purposes. The subjects also were given only water and were studied over the same time period (water control). Plasma glucose, glucagon, alpha-amino nitrogen, nonesterified fatty acids, serum insulin, C-peptide, and triglyceride concentrations were determined over 5 h. The integrated area responses were quantified over the 5-h period using the water control as a baseline.

RESULTS— The mean plasma glucose area response after ingestion of potato with or without the various amounts of butter were all similar and were 82% of that observed after ingestion of 50 g glucose. The mean insulin area response to potato alone was 532 pmol · h · L−1. The mean insulin area responses to potato plus 5,15,30, and 50 g of fat meals were 660,774,750, and 756 pmol · h · L−1, respectively. Thus, the mean insulin areas were all greater than for ingestion of potato alone, and a maximal response was observed with addition of 15 g fat (1.4-fold). The C-peptide data did not confirm an increase in insulin secretion. Overall the area responses after ingestion of meals containing fat were not different from the response to potato ingestion alone, although the responses were erratic. The glucagon area response was positive after ingestion of all fat containing meals except for that containing only 5 g fat, and there was a dose-response relationship. The plasma alpha-amino nitrogen and nonesterified fatty acid area responses were negative after potato ingestion and were not significantly different when fat was added. The serum triglyceride concentration increase was greater after the ingestion of butter with the potato as expected.

CONCLUSIONS— In contrast to the results in normal subjects after ingestion of butter with potato, the glucose response was not smaller in subjects with NIDDM. The insulin response was greater. The insulin area response data indicated the presence of a dose-response relationship. Whether similar responses will be observed with other dietary fat and CHO sources remains to be determined.
Severe Insulin-Induced Lipohypertrophy Successfully Treated by Liposuction
Authors: Hardy Kevin J , Gill Geoffrey V , Bryson J Richard
Published: March 2007

OBJECTIVE— To examine the usefulness of liposuction surgery on diabetic patients with lipohypertrophy.

RESEARCH DESIGN AND METHODS— We treated a diabetic patient who suffered from severe localized thigh lipohypertrophy. When she did not respond to conventional treatment of resting the injection site, we recommended liposuction surgery.

RESULTS— Our patient's lipohypertrophy was immediately cured by the liposuction procedure.

CONCLUSIONS— Liposuction surgery could be useful in patients with diabetic lipohypertrophy who do not respond to more conservative treatments.
Smell Dysfunction and Related Factors in Diabetic Patients
Authors: Le Floch Jean-Pierre , Le Lièvre Gilles , Labroue Michael , Paul Muriel , Peynegre Roger , Perlemuter Leon
Published: March 2007

OBJECTIVE— To analyze smell function in diabetic patients and healthy control subjects, with reference to individual characteristics and major complications of the disease.

RESEARCH DESIGN AND METHODS— A cross-sectional study of smell recognition in 68 diabetic patients and 30 control subjects without known cause of smell impairment was conducted. Smell was studied using a kit of flavors that patients were asked to recognize, leading to a smell recognition score ranging from 0 (no recognition) to 20 (perfect recognition). Demographic and clinical data, and the electrogustometric threshold were recorded in both groups. Metabolic control and degenerative complications were studied in diabetic patients.

RESULTS— The SRS was significantly lower in diabetic patients than in control subjects (12.4 ± 0.5 vs. 15.1 ± 0.5, P < 0.001). By use of univariate and multivariate analyses, this difference could not be explained by individual factors such as age, sex, body mass index, blood pressure, or tobacco or alcohol consumption but was related to diabetes. SRS correlated with EGT (r = 0.70, P < 0.001). In the diabetic group, SRS was associated with age (r = 0.29, P < 0.05), duration of diabetes (r = 0.27, P < 0.05), microalbuminuria (12.2 ± 0.8 vs. 14.4 ± 0.9, P < 0.05), peripheral neuropathy (10.3 ± 1.0 vs. 14.1 ± 0.9, P < 0.01), and EGT (r = 0.39; P < 0.001). By use of multivariate analysis, the strongest association was found with EGT (R2 = 0.15).

CONCLUSIONS— These results suggest that smell recognition is impaired in patients with diabetes mellitus. Smell dysfunction is associated with age and degenerative complications of diabetes, suggesting a degenerative mechanism related to diabetes.
Evidence for a Role for Insulin and Growth Hormone in Overnight Regulation of 3-Hydroxybutyrate in Normal and Diabetic Adolescents
Authors: Edge Julie A , Harris Dorothy A , Phillips Paula E , Pal B Rani , Matthews David R , Dunger David B
Published: March 2007

Objective— To determine the relative effects of growth hormone and insulin on ketogenesis during puberty.

Research Design and Methods— We studied overnight changes in plasma ketones—3-hydroxybutyrate and acetoacetate—in 35 normal and 26 IDDM adolescents at different stages of puberty. The diabetic adolescents either were on their normal insulin regimen or were studied during an overnight euglycemic clamp with or without suppression of endogenous growth hormone release.

Results— Total ketone body and 3-hydroxybutyrate concentrations in the normal adolescents rose significantly from 2000 (29 ± 5 μM), reaching a peak at 0200 (103 ± 16 μM, P < 0.001 vs. 2000). After a brief fall, a further rise occurred before breakfast. Fasting 3-hydroxybutyrate concentrations showed a negative correlation with fasting insulin levels (r = −0.46, P = 0.005) and decreased with advancing puberty, while insulin concentrations increased. In the diabetic patients on their usual insulin regimen, free insulin levels waned overnight, and an exaggerated rise in ketones was observed before breakfast. During the euglycemic clamp studies, ketone levels were higher than normal throughout the night. Mean overnight growth hormone and free insulin levels also were higher than in the normal control subjects. The addition of the anticholinergic drug pirenzepine reduced growth hormone secretion and obliterated the early-night peak of 3-hydroxybutyrate.

Conclusions— We conclude that the early-night peak of ketone concentrations is related to growth hormone release, whereas the fasting levels are largely determined by insulin concentration. Inadequate insulin delivery in the presence of the high growth hormone concentrations characteristic of diabetic adolescents could lead to rapid decompensation and ketoacidosis.
Seven Years of Remission in a Type I Diabetic Patient: Influence of cyclosporin and regular exercise
Authors: Koivisto Veikko A , Leirisalo-Repo Marjatta , Ebeling Pertti , Tuominen Juha A , Knip Mikael , Turunen Ulla , Mandrup-Poulsen Thomas , Pelkonen Risto
Published: March 2007

Objective— To analyze factors contributing to a long-term remission in a patient with type I diabetes.

Research Design and Methods— The patient was treated with cyclosporin for 16 mo after a short duration of symptoms. During the 7-yr follow-up, we tracked his glycemic control, oral glucose tolerance, insulin sensitivity, endogenous insulin secretion, and β-cell immunology. The results are compared with those of matched diabetic patients and healthy control subjects.

Results— Insulin therapy was discontinued after 5 wk. Thereafter the patient had normal fasting and home blood glucose concentrations and near-normal HbA1c without insulin therapy for 7 yr. During this period, he maintained islet cell antibodies, although his basal and glucagon-stimulated C-peptide concentrations were normal. He participated in active physical training and had an insulin sensitivity higher than in sedentary control subjects or trained diabetic patients and equal to that in healthy athletes. His oral glucose tolerance decreased gradually and became diabetic during the last 3 yr.

Conclusions— In this patient, an early start of cyclosporin therapy probably contributed to the maintenance of endogenous insulin secretion, and insulin sensitivity was high because of physical training. Consequently, the patient was able to maintain normoglycemia without exogenous insulin therapy for 7 yr.
Glycemic Actions of Alanine and Terbutaline in IDDM
Authors: Wiethop Brian V , Cryer Philip E
Published: March 2007

OBJECTIVE

To test the hypothesis that the amino acid Ala and the beta 2-adrenergic agonist terbutaline raise plasma glucose concentrations substantially, and do so through different mechanisms, in IDDM patients.

RESEARCH DESIGN AND METHODS

We administered these (Ala: 20 and 40 g, orally; terbutaline: 2.5 and 5.0 mg orally and 0.25 mg subcutaneously) and placebos in random sequence to 6 nondiabetic subjects and 6 insulin-infused, initially euglycemic IDDM patients, each studied on six different occasions. Inhaled terbutaline, 0.4 mg, was also tested on a seventh occasion in IDDM patients.

RESULTS

Ala administration raised plasma glucagon (P = 0.0219), C-peptide (P = 0.0014), and insulin (P = 0.0094), with no significant change in plasma glucose, in nondiabetic subjects. In patients with IDDM it raised glucagon (P = 0.0001), but not C-peptide or insulin, and plasma glucose rose to 8.3 ± 0.3 (Ala 20 g, P = 0.0006) and 10.0 ± 1.0 mM (Ala 40 g, P = 0.0094). Catecholamine levels were unchanged. Terbutaline ingestion raised plasma glucose minimally (e.g., to 6.3 ± 0.3 mM, P = 0.0133) in nondiabetic subjects but substantially, to 10.2 ± 1.0 (terbutaline 2.5 mg, P = 0.0078) and 14.0 ± 0.6 mM (terbutaline 5.0 mg, P = 0.0001), in IDDM patients; subcutaneous terbutaline raised plasma glucose (to a peak of 10.3 ± 0.7 mM, P = 0.0017) with an initial effect within 10 min, but inhaled terbutaline did so more slowly. In addition to its direct glycemic actions, terbutaline stimulated sympathetic neural norepinephrine release (P = 0.0151) and increased nonesterified fatty acid levels (P = 0.0104), potential indirect glycemic actions. Glucagon levels were unchanged; insulin levels increased in the nondiabetic subjects.

CONCLUSIONS

These data demonstrate substantial glycemic responses to Ala and terbutaline, through different mechanisms, in IDDM patients. Thus, Ala and terbutaline represent potential new approaches to the treatment, and perhaps the prevention, of iatrogenic hypoglycemia in IDDM.
Prevalence of Depression in Adults With Diabetes: An epidemiological evaluation
Authors: Gavard Jeffrey A , Lustman Patrick J , Clouse Ray E
Published: March 2007

OBJECTIVE

To determine the prevalence of depression in adult diabetic populations through a comprehensive literature review and to critically evaluate the methods and findings of such studies from an epidemiological perspective.

RESEARCH DESIGN AND METHODS

A systematic review of the scientific literature revealed a total of 20 studies, 14 of which had been conducted since 1988. Nine of the studies were controlled investigations, whereas the remaining 11 studies did not contain comparison groups. The studies included both treatment and community samples.

RESULTS

The range of the prevalence of current depression obtained from structured diagnostic interviews in diabetic samples was 8.5–27.3% ( = 14.0%) in controlled studies and 11.0–19.9% ( = 15.4%) in uncontrolled studies. These rates are at least three times the prevalence of major depressive disorder found in the general adult population of the U.S. Investigations using depression symptom scales corroborated these findings, as the range of clinically significant depression symptomatology in diabetic samples was 21.8–60.0% ( = 32.4%) in controlled studies and 10.0–28.0% ( = 19.6%) in uncontrolled studies.

CONCLUSIONS

An increased prevalence of depression in diabetes relative to the general population is highly suggested by the literature, but biases and methodological problems commonly encountered in prevalence studies may interfere with the strength of this conclusion. An increased prevalence of depression in diabetes relative to other somatic illnesses remains unproven. The pervasive impact of depression on quality of life and its potential negative effect on diabetes management warrant recognition and treatment of the affective disorder in diabetic individuals.
Effectiveness, Safety, and Acceptability of a Copper Intrauterine Device (CU Safe 300) in Type I Diabetic Women
Authors: Kimmerle Renate , Weiss Reinhard , Berger Michael , Kurz Karl-Heinz
Published: March 2007

Objective— To evaluate the long-term effectiveness and safety of a copper intrauterine device fulfilling modern standards in type I diabetic women compared with nondiabetic women.

Research Design and Methods— Type I diabetic women (n = 59, age 27 ± 5 yr, duration of diabetes 12 ± 8 yr, HbA1c 7.0 ± 1.2%, 78% nulliparous women) were prospectively evaluated at 3, 6, 12, 24, and 36 mo by a gynecological exam and a standardized questionnaire after insertion of the intrauterine device (CU Safe 300, 300 mm2 of copper). A group of nondiabetic women (n = 1150) of comparable age and parity evaluated according to the same study protocol served as a control group.

Results— In the diabetic women (1754 cumulative months of use), events leading to termination of the intrauterine device during the 1st yr (691 women-mo) were one accidental pregnancy, one expulsion, one removal for pain, two removals for bleeding, and one removal for planned pregnancy. Events during the 2nd (593 women-mo) and 3rd yr (470 women-mo) were zero and one accidental pregnancy., one and two removals for bleeding, one and one removal for pain, one and one removal for other medical reasons, and two and two removals for planned pregnancy, respectively. No case of pelvic inflammatory disease was diagnosed in the diabetic group, and one case was diagnosed in the nondiabetic group (28,369 mo of cumulative use). Events leading to termination of the intrauterine device per women observed per year and continuation with the intrauterine device after each year of use were comparable in the diabetic and nondiabetic groups for the 1st, 2nd, and 3rd yr.

Conclusions— These results, although preliminary because < 100 diabetic women were studied, indicate that the intrauterine device CU Safe 300 is as effective, safe, and well-tolerated in diabetic as in nondiabetic women. Specific objections to the use of intrauterine devices in type I diabetic women do not seem to be justified for modern, copper-mediated models.
Administration of Sulfonylureas Can Increase Glucose-Induced Insulin Secretion for Decades in Patients With Maturity-Onset Diabetes of the Young
Authors: Fajans Stefan S , Brown Morton B
Published: March 2007

Objective— To ascertain whether the effect of sulfonylureas on glucose-mediated insulin release persists for years to decades in patients with maturity-onset diabetes of the young.

Research Design and Methods— The effect of sulfonylurea treatment on glucose-induced insulin secretion was ascertained prospectively for up to 33 yr in 12 diabetic patients of the maturity-onset diabetes of the young RW pedigree, who are genetically homogeneous because they share DNA markers on chromosome 20q. In 7 of these patients, paired glucose tolerance tests, given while the patients were on and off sulfonylureas, were performed after 7–31 yr.

Results— Glucose-induced insulin secretion showed an average increase of 68% in diabetic patients who remained responsive to chlorpropamide after having been on and off the drug for decades. In most patients, however, glucose-induced insulin secretion declines over time (1–4%/yr). Some patients become unresponsive to sulfonylureas after 3–25 yr and then have very small or no increases in glucose-induced insulin secretion and require treatment with insulin to normalize fasting hyperglycemia.

Conclusions— Increase in glucose-induced insulin secretion remains the most important mechanism of the action of sulfonylureas during long-term administration.
Differences in the Prevalence of Diabetes and Impaired Glucose Tolerance According to Maternal or Paternal History of Diabetes
Authors: Mitchell Braxton D , Valdez Rodolfo , Hazuda Helen P , Haffner Steven M , Monterrosa Ana , Stern Michael P
Published: March 2007

Objective— To determine whether diabetes risk is influenced by which parent (a parental history of diabetes is a well-documented risk factor for NIDDM) is reported to have diabetes.

Research Design and Methods— We compared the prevalence of NIDDM and IGT for 4914 subjects according to their parental history of diabetes (mother only, father only, both parents, neither parent). Subjects were drawn from the San Antonio Heart Study, a population-based survey of diabetes and cardiovascular risk factors conducted in Mexican American and non-Hispanic white individuals between 1979–1988.

Results— Men with a parental history of diabetes had a higher prevalence of both NIDDM and impaired glucose tolerance than men reporting no parental history of diabetes. Prevalence was equally high regardless of which parent, or whether both parents, had diabetes. In contrast, in women, only a maternal history of diabetes was associated with a higher prevalence of NIDDM and impaired glucose tolerance. Virtually no difference in NIDDM prevalence was found between women with a paternal-only history of diabetes and women with no parental history of diabetes.

Conclusions— Results differed markedly between men and women. The reason for this sex difference is unclear. It may represent a measurement bias, a sex-specific environmental effect, or a genetic effect that is expressed or transmitted differently between the sexes.
Cow's Milk Exposure and Type I Diabetes Mellitus: A critical overview of the clinical literature
Authors: Gerstein Hertzel C
Published: March 2007

OBJECTIVE

To critically review and summarize the clinical evidence relating a short duration of breast-feeding or early cow's milk exposure to insulin-dependent (type I) diabetes.

RESEARCH DESIGN AND METHODS

All relevant citations retrieved through comprehensive searching of the medical literature were critically reviewed and analyzed. Those case-control studies that minimized the possibility of bias were meta-analyzed to determine overall odds ratios (ORs) and 95% confidence intervals (CIs).

RESULTS

Ecological and time-series studies consistently showed a relationship between type I diabetes and either cow's milk exposure or diminished breast-feeding. In the case-control studies, patients with type I diabetes were more likely to have been breast-fed for <3 months (overall OR 1.43; 95% CI 1.15–1.77) and to have been exposed to cow's milk before 4 months (overall OR 1.63; 95% CI 1.22–2.17). Slightly lower ORs were obtained when all of the case-control studies were metaanalyzed in a sensitivity analysis.

CONCLUSIONS

Early cow's milk exposure may be an important determinant of subsequent type I diabetes and may increase the risk ∼1.5 times.
Effects of the Carbohydrase Inhibitor Miglitol in Sulfonylurea-Treated NIDDM Patients
Authors: Johnston Peter S , Coniff Robert F , Hoogwerf Byron J , Santiago Julio V , Pi-Sunyer F Xavier , Krol Alice
Published: March 2007

OBJECTIVE

To examine the effects of the carbohydrase inhibitor miglitol (BAY m 1099) on the metabolic profiles of non-insulin-dependent diabetes mellitus (NIDDM) patients suboptimally controlled on maximal daily doses of sulfonylurea (SFU) agents.

RESEARCH DESIGN AND METHODS

Multicenter, double-blind, randomized, placebo-controlled 14-week clinical trial with six-week, single-blind placebo lead-in and run-out periods. NIDDM volunteers (192) with fasting plasma glucose (FPG) 140–250 mg/dl and hemoglobin A1c (HbA1c) 6.5–12.0% after at least 4 weeks of treatment with SFU at maximal dose were stratified by baseline HbA1c (above and below 9.0%) and then randomly assigned within strata to placebo (n = 63), 50 mg miglitol 3 times a day (n = 61), or 100 mg miglitol 3 times a day (n = 68). Efficacy was assessed by HbA1c, FPG, insulin, and lipid concentrations, and by plasma glucose and serum insulin responses to a standard meal.

RESULTS

In the 50 and 100 mg miglitol treatment groups, the mean changes from baseline in HbA1c (with placebo values subtracted) were 0.82 and 0.74%, respectively, and were highly significant (P = 0.0001 in each case). Mean peak plasma glucose levels after a standard test meal were comparably lowered by 57 mg/dl with the 50 mg miglitol dose, and by 64 mg/dl with the 100 mg miglitol dose compared with placebo (P = 0.0001 for each), with associated reductions in integrated serum insulin response (P < 0.05). No significant drug-associated changes in FPG, insulin, or cholesterol levels were noted, but fasting triglyceride levels were lowered significantly with the 50 mg miglitol dose. Miglitol's side effects were limited to flatulence, loose stools, and abdominal discomfort, which were dose-related, rapidly resolved on drug discontinuation, and led to withdrawal from the study of 5 and 15% of patients taking 50 and 100 mg miglitol, respectively.

CONCLUSIONS

Miglitol may be indicated as effective adjuvant therapy in NIDDM patients with suboptimal metabolic control despite conventional treatment with diet and maximal daily doses of SFU. The dose of 50 mg miglitol 3 times a day may be preferable to 100 mg miglitol 3 times a day because of comparable efficacy and substantially reduced side effects.
Dietary Fat Predicts Conversion From Impaired Glucose Tolerance to NIDDM: The San Luis Valley Diabetes Study
Authors: Marshall Julie A , Hoag Sharon , Shetterly Susan , Hamman Richard F
Published: March 2007

OBJECTIVE

To determine if dietary fat intake measured at a baseline exam in subjects with impaired glucose tolerance (IGT) predicted the subsequent development of non-insulin-dependent diabetes mellitus (NIDDM).

RESEARCH DESIGN AND METHODS

Based on an oral glucose tolerance test (OGTT) (World Health Organization criteria), we identified 134 eligible subjects with IGT from a geographically based sample of subjects with no prior history of diabetes. One to three years after the baseline exam, 123 subjects (92%) had a repeat OGTT. Diet was assessed by a 24-h diet recall reported before the baseline OGTT.

RESULTS

The mean percentage of energy eaten as fat was 43.4% in 20 people subsequently developing NIDDM compared with 40.6% in 43 people remaining IGT and 38.9% in 60 subjects who subsequently reverted to normal glucose tolerance. In comparing the 20 subjects who developed NIDDM with the 103 who remained IGT or normal, an increase in fat intake of 40 g/day was associated with an increase in risk of NIDDM of 3.4-fold (95% confidence interval [CI] 0.8–13.6) adjusted for energy intake, age, sex, ethnicity, and obesity. The odds ratio increased to sixfold (95% CI 1.2–29.8) after adjustment for fasting glucose, insulin, and 1-h insulin.

CONCLUSIONS

Fat consumption significantly predicts NIDDM risk in subjects with IGT after controlling for obesity and markers of glucose metabolism.
Effect of Metformin on Postprandial Lipemia in Patients With Fairly to Poorly Controlled NIDDM
Authors: Jeppesen Jorgen , Zhou Ming-Yue , Chen Y-D Ida , Reaven Gerald M
Published: March 2007

OBJECTIVE

To quantify the effect of metformin on the metabolism of triglyceride (TG)-rich lipoprotein of intestinal origin in patients with non-insulin-dependent diabetes mellitus (NIDDM) who had responded to sulfonylurea but still had fasting hyperglycemia.

RESEARCH DESIGN AND METHODS

Sixteen patients with NIDDM who had demonstrated a fall in fasting plasma glucose concentration > 2.2 mmol/l in response to glipizide treatment but continued to have fasting plasma glucose concentrations > 8.3 mmol/l were studied. Fasting glucose, GHb, lipid and lipoprotein concentrations were determined, and resistance to insulin-mediated glucose disposal was estimated by measuring the steady-state plasma glucose (SSPG) concentration at the end of a 180-min infusion of somatostatin, glucose, andinsulin. In addition, plasma glucose, insulin, and TG concentrations were measured at frequent intervals from 0800 to 2400, with patients eating breakfast at 0800 and lunch at 1200. Vitamin A was also given at lunch, and the retinyl ester content in plasma and in chylomicron (Svedberg flotation constant [Sr] > 400) and the chylomicron remnant (Sr 20–400) fractions were used to quantify the concentration of postprandial intestinal TG-rich lipoprotein from 1200 to 2400.

RESULTS

Fasting plasma glucose concentrations (6.8 ± 0.4 vs. 10.5 ± 0.4 mmol/l), GHb levels (7.9 ± 0.3 vs. 10.8 ± 0.5%), and day-long plasma glucose concentrations were all significantly lower after metformin treatment (P < 0.001), which was associated with a significant (P < 0.001) fall in SSPG concentration (11.0 ± 0.9 to 9.6 ± 0.6 mmol/l). In addition, postprandial concentrations of glucose, insulin, free fatty acids, and TG were lower (P < 0.001) following metformin treatment. Postprandial retinyl ester concentrations were also lower in plasma by 33 ± 5.7% (P < 0.001) and in both the chylomicron (32 ± 7.2%, P < 0.001) and chylomicron remnant (26 ± 7.0%, P < 0.005) fractions.

CONCLUSIONS

Addition of metformin to sulfonylurea-treated patients with NIDDM with less than optimal glycemic control was associated with improved glycemic control, lower postprandial insulin and TG concentrations, and a decrease inpostprandial concentration of TG-rich lipoproteins of intestinal origin. All of these changes might be expected to decrease risk of coronary heart disease.
The Relationship Between Serum Lipoprotein(a) and Insulinemia in Healthy Nondiabetic Adult Men
Authors: Duell P Barton , Hagemenas Fay , Connor William E
Published: March 2007

OBJECTIVE

To test the hypothesis that variations in serum insulin concentrations and insulin action may influence serum concentrations of lipoprotein(a) [Lp(a)].

RESEARCH DESIGN AND METHODS

A cross-sectional analysis of fasting serum insulin and Lp(a) concentrations were conducted in a group of 54 healthy adult men 23–61 years of age. Measures of dietary intake, exercise, smoking, alcohol ingestion, body mass index (BMI), fasting plasma lipoprotein lipid concentrations, and serum sex hormone and fasting glucose levels were also determined.

RESULTS

The fasting serum concentrations of insulin and Lp(a) were negatively correlated (r = −0.339, P = 0.014) by univariate regression analysis. Several confounding variables were also significantly correlated with Lp(a) concentrations: testosterone (r = 0.348, P = 0.012), strenuous exercise (r = 0.287, P = 0.041), and BMI (r = −0.276, P = 0.050). As expected, these additional variables and serum insulin concentrations were highly interrelated. In a stepwise regression model, the serum insulin level was identified as the single best predictor of Lp(a) levels. Nearly 25% of the heterogeneity in serum concentrations of Lp(a) could be predicted by serum levels of insulin and testosterone, BMI, and the amount of strenuous exercise.

CONCLUSIONS

The results of these studies have shown that serum concentrations of insulin and testosterone, BMI, and strenuous exercise appear to account for the majority of predicted nongenetic variability in serum levels of Lp(a). These observations suggest the possibility in this group of healthy men that serum concentrations of Lp(a) may be modulated by a complex interplay between insulin action, obesity, androgen levels, and strenuous exercise.
Effects of Postprandial Exercise on Glycemic Response in IDDM Subjects: Studies at constant insulinemia
Authors: Rasmussen Ole W , Lauszus Finn F , Hermansen Kjeld
Published: March 2007

OBJECTIVE

To determine the influence of postprandial exercise on blood glucose responses in insulin-dependent diabetes mellitus (IDDM) subjects.

RESEARCH DESIGN AND METHODS

Two identical test meals were served with a 7-day interval. On one occasion, a 30-min cycle exercise was performed 15 min after the meal. Patients had achieved normoglycemia by means of an artificial pancreas (Biostator) before the meals, which also ensured constant insulin infusion in the study periods. Seven IDDM subjects attending the outpatient clinic at Aarhus Kommunehospital were studied.

RESULTS

The 30 min of cycling reduced postprandial blood glucose response areas by 34 ± 12% (P < 0.01) from 638 ± 30 to 492 ± 61 mmol/l × 180 min (P < 0.03), whereas similar peak blood glucose values were found (13.7 ± 0.3 vs. 12.0 ± 1.3 mmol/l).

CONCLUSIONS

Thirty minutes of moderate exercise done postprandially reduces the blood glucose response to 50 g carbohydrate by about one-third.
A Practical Two-Step Quantitative Clinical and Electrophysiological Assessment for the Diagnosis and Staging of Diabetic Neuropathy
Authors: Feldman Eva L , Stevens M J , Thomas P K , Brown M B , Canal N , Greene D A
Published: March 2007

OBJECTIVE

Early diagnosis of distal symmetric sensorimotor polyneuropathy, a common complication of diabetes, may decrease patient morbidity by allowing for potential therapeutic interventions. We have designed an outpatient program to facilitate diagnosis of diabetic neuropathy.

RESEARCH DESIGN AND METHODS

Patients are initially administered a brief questionnaire and screening examination, designated the Michigan Neuropathy Screening Instrument (MNSI). Diabetic neuropathy is confirmed in patients with a positive assessment by a quantitative neurological examination coupled with nerve conduction studies, designated the Michigan Diabetic Neuropathy Score (MDNS). In this study, 56 outpatients with confirmed type I or II diabetes were administered the standardized quantitative components required to diagnose and stage diabetic neuropathy according to the San Antonio Consensus Statement (1) and the Mayo Clinic protocol (2). These same patients were then assessed with the MNSI and the MDNS.

RESULTS

Of 29 patients with a clinical MNSI score > 2, 28 had neuropathy. Twenty-eight patients with an MDNS of ≥ 7 had neuropathy, while 21 non-neuropathic patients had a score ≤ 6. Of 35 patients with diabetic neuropathy, 34 had ≥ 2 abnormal nerve conductions. Twenty-one normal patients and one patient with neuropathy had ≤ 1 abnormal nerve conduction.

CONCLUSIONS

The results indicate that the MNSI is a good screening tool for diabetic neuropathy and that the MDNS coupled with nerve conductions provides a simple means to confirm this diagnosis.
Intraperitoneal Insulin Delivery Decreases the Levels of Chylomicron Remnants in Patients With IDDM
Authors: Georgopoulos Angeliki , Saudek Christopher D
Published: March 2007

OBJECTIVE

To investigate whether intraperitoneal insulin (IPII) decreases the levels of circulating chylomicron remnants in patients with insulin-dependent diabetes mellitus (IDDM).

RESEARCH DESIGN AND METHODS

Eight nonobese, normolipidemic IDDM patients were studied twice: before (while on subcutaneous insulin) and 6 months after initiation of IPII by a programmable implanted medication system. Fasting and mean blood glucose, HbA1, and lipid values were determined. Blood samples were also drawn before and every 2 h for 10 h after ingestion of a fat meal (corn oil + Vitamin A). Triglycerides (TGs), apolipoprotein B (apoB), and retinyl esters were determined over time in two TG-rich lipoprotein subfractions (Sf > 100 and Sf20−100) isolated from plasma by density-gradient ultracentrifugation.

RESULTS

IPII slightly decreased the mean blood glucose from 7.8 ± 1.1 to 7.4 ± 1.1 mmol/l (mean ± SD, P = 0.027, paired Student's t test) and the HbA1 from 9.4 ± 1.5 to 8.7 ± 1.2 (NS). TG and apoB levels in postprandial Sf > 100 and Sf20–100 were not changed by IPII. On IPII, however, retinyl ester levels in Sf > 100 decreased (P = 0.05, analysis of variance [ANOVA]) and tended to be lower in Sf20–100 (P = 0.075). In addition, following IPII, the retinyl ester:apoB ratio was lower in Sf > 100 (P = 0.0002) and marginally lower (P = 0.06) in Sf 20–100.

CONCLUSIONS

IPII decreased chylomicron remnant levels, which might decrease the atherosclerotic risk in IDDM. Since glycemic control was only slightly improved, the effect was most likely due to the intraperitoneal route of delivery.
Human Leukocyte Antigen Class II Polymorphisms and Genetic Susceptibility of IDDM in Egyptian Children
Authors: Gaber Samir A , Mazzola Gina , Berrino Monica , Canale Lorena , Cornaglia Maura , Ghali Isis , Curtoni Emilio Sergio , Amoroso Antonio
Published: March 2007

OBJECTIVE

To analyze the association between human leukocyte antigen (HLA) and insulin-dependent diabetes mellitus (IDDM) in the Egyptian population for the first time and, thus, to determine the frequency of risk-associated alleles identified by a genomic HLA class II typing. Egyptians are genetically classified as North Africans and considered to be between Caucasoids and Africans (closer to Caucasoids).

RESEARCH DESIGN AND METHODS

HLA class II typing was performed for 50 IDDM patients and 50 healthy control subjects by a restriction fragment-length polymorphism (RFLP) technique. The analysis of position 57 of the DQB1 molecules was conducted by polymerase chain reaction and specific sequence oligonucleotide hybridization.

RESULTS

The frequency of DRB1*0301-DRB3*0201-DQA1*0501-DQB1*0201 haplotype was 43.9% in the IDDM patients and 7.1% in the control subjects (P < 0.00001), reflecting the increased prevalence of DQA1*0501 susceptibility allele coding for arginine (Arg) in position 52 and DQB1*0201 susceptibility allele non-coding aspartic acid (Asp) at position 57. Alleles DQB1*0601 and 0603, both carrying Asp at position 57 of the β-chain, and DQA1*0103, encoding a non-Arg 52 alpha-chain, were significantly decreased among the IDDM patients. The presence of four susceptibility residues (two DQA1 Arg 52+ and two DQB1 Asp 57−) conferred the highest relative risk at 20.2. On the other hand, homozygous genotypes for DQA1 non-Arg 52 and DQB1 Asp 57 were found only in the control group.

CONCLUSIONS

IDDM susceptibility and resistance in the Egyptian population is strongly associated with the expressed DQ α- and β-heterodimers in a dose-effective manner, as already defined in many different ethnic groups.
Beneficial Effect of Chromium Supplementation on Serum Triglyceride Levels in NIDDM
Authors: Lee Nancy A , Reasner Charles A
Published: March 2007

OBJECTIVE

To investigate the effect of chromium picolinate supplementation on the lipid profile of the predominantly Hispanic population of non-insulin-dependent diabetes mellitus (NIDDM) patients in San Antonio, Texas.

RESEARCH DESIGN AND METHODS

A prospective, double-blind, placebo-controlled, crossover study was performed on 14 men and 16 women. Initially, each patient was randomly assigned to receive either chromium picolinate or placebo for 2 months. This initial treatment phase was followed by a 2-month washout period. Subjects were then crossed-over and received the alternate capsule for an additional 2 months. Fasting blood glucose, HbA1c, and serum lipids were compared at the end of each treatment phase.

RESULTS

Twenty-eight of the originally enrolled 30 patients completed the study. There were no adverse reactions to chromium reported. There were no differences noted between the control and chromium-treated subjects in glucose control, high-density lipoprotein cholesterol levels, or low-density lipoprotein cholesterol levels. Triglyceride (TG) levels were reduced significantly (17.4%; P < 0.05) during the 2 months of chromium supplementation.

CONCLUSIONS

Ours is the first report of a significant reduction in serum TGs in a group of NIDDM patients treated with chromium. The low cost and excellent safety profile of chromium make it an attractive lipid-lowering agent for this population. Long-term studies are needed to determine if the short-term changes in plasma lipids can be sustained.
Lower Prevalence of Impaired Glucose Tolerance and Diabetes Associated With Daily Seal Oil or Salmon Consumption among Alaska Natives
Authors: Adler Amanda I , Boyko Edward J , Schraer Cynthia D , Murphy Neil J
Published: March 2007

OBJECTIVE

To examine the association of seal oil and salmon consumption with impaired glucose tolerance (IGT) and non-insulin-dependent diabetes mellitus (NIDDM) among Alaska Natives.

RESEARCH DESIGN AND METHODS

Screening was performed on 666 Yup'ik Eskimos and Athabaskan Indians ≥40 years old in 15 villages. Self-administered questionnaires were used to obtain partial food frequency data. A case was defined as IGT or NIDDM, either newly discovered or known. Newly discovered cases (11 patients with NIDDM and 17 with IGT) were determined by random blood glucose testing followed by a 2-h 75-g oral glucose tolerance test (OGTT) for those with values ≥ 6.72 mmol/l or for subjects with unconfirmed histories of glucose intolerance. Known cases included 26 patients with NIDDM and 1 with IGT. Control subjects had random blood glucoses <6.72 or normal OGTT results.

RESULTS

Compared with less-than-daily consumption, both daily seal oil (odds ratio [OR] 0.2, 95% confidence interval [CI] 0.1–0.8) and daily salmon consumption (OR 0.5, CI 0.2–1.1) were associated with a lower prevalence of glucose intolerance, controlling for age, ethnicity, body mass index, and sex. The effects were similar when limited to newly discovered cases: OR 0.3, CI 0.1–1.3 for seal oil and OR 0.4, CI 0.1–1.3 for salmon. Consumption of seal oil at least five times per week was required to reduce risk.

CONCLUSIONS

Consumption of seal oil and salmon, high in ω-3 fatty acids, appears to lower the risk of glucose intolerance and is a potentially modifiable risk factor for NIDDM in Alaska Natives.
Light-to-Moderate Alcohol Intake Is Associated With Enhanced Insulin Sensitivity
Authors: Facchini Francesco , Ida Chen Y-D , Reaven Gerald M
Published: March 2007

OBJECTIVE

To test the hypothesis that insulin-mediated glucose uptake is enhanced in light-to-moderate alcohol consumption.

RESEARCH DESIGN AND METHODS

This is a case-control study of healthy volunteers, divided into nondrinkers and light-to-moderate drinkers based on their history of alcohol consumption. The study was performed at the General Clinical Research Center at Stanford University Medical Center and involved 40 volunteers, 20 men and 20 women. Measurements were made of the plasma glucose and insulin responses to an oral glucose challenge, fasting plasma lipid and lipoprotein concentrations, and steady-state plasma insulin (SSPI) and steady-state plasma glucose (SSPG) concentrations in response to a continuous infusion of somatostatin, insulin, and glucose.

RESULTS

Light-to-moderate drinkers (10-30 g/day) had lower integrated plasma glucose (17.8 ± 0.8 vs. 19.8 ± 0.9 mM/h, P < 0.02) and insulin (600 ± 65 vs. 1,075 ± 160 pM/h, P < 0.01) responses to the glucose challenge and higher fasting plasma high-density lipoprotein (HDL) cholesterol concentrations (1.46 ± 0.08 vs. 1.25 ± 0.08, P ± 0.02). Despite similar SSPI concentrations of ∼300 pM, SSPG concentrations were lower (P ± 0.01) in light-to-moderate drinkers (6.7 ± 0.8 vs. 10.7 ± 1.2 mM). Results were independent of age, body mass index, ratio of waist-to-hip girth, and estimates of level of habitual physical activity.

CONCLUSIONS

Light-to-moderate alcohol consumption in healthy men and women is associated with enhanced insulin-mediated glucose uptake, lower plasma glucose and insulin concentrations in response to oral glucose, and a higher HDLcholesterol concentration. The changes in glucose and insulin metabolism may contribute to the lower risk of coronary heart disease described in light-to-moderate drinkers.