bluuebunny/crossref_metadata_2025 huggingface dataset:
Results of a Placebo-Controlled Study of the Metabolic Effects of the Addition of Metformin to Sulfonylurea-Treated Patients: Evidence for a central role of adipose tissue
Authors: Abbasi Fahim , Kamath Vinaya , Rizvi Ali A , Carantoni Marcello , Chen Y D I , Reaven Gerald M
Published: March 2007

OBJECTIVE

To define the metabolic effects of metformin in the treatment of NIDDM and to evaluate potential mechanisms for its ability to improve glycemic control.

RESEARCH DESIGN AND METHODS

Sulfonylurea-treated patients, with inadequate glycemic control, were treated with metformin in either a placebo-controlled or open fashion. Measurements were made of 1) fasting and postprandial plasma glucose, insulin, and free fatty acid (FFA) concentrations; 2) glucose appearance and disappearance rates measured overnight with 3-[3H]glucose; and 3) plasma FFA concentrations during a 45-min infusion period at relatively low (∼ 60 pmol/l) insulin concentrations.

RESULTS

Mean ± SE hourly plasma glucose, insulin, and FFA concentrations were similar before and after treatment in the placebo group. In contrast, mean hourly plasma glucose concentrations were significantly lower (P < 0.005) after metformin treatment in both the placebo-controlled and open-label groups (−3.9 ± 1.0 and −4.4 ± 0.8 mmol/l, respectively). Similarly, day-long hourly FFA levels were lower (P < 0.005) following metformin in the placebo-controlled and open-label groups (−87 ± 35 and −136 ± 31 μmol/l, respectively). Plasma insulin concentrations did not change with treatment in any group. Overnight glucose turnover studies indicated that neither the rate of glucose appearance (hepatic glucose production) or glucose disappearance changed significantly with treatment in the placebo or metformin groups. Because plasma glucose concentration was much lower after metformin treatment, overnight glucose metabolic clearance rate was significantly (P < 0.001) lower in this group. Finally, plasma FFA concentrations in response to a low-dosage insulin infusion (5 mU · m−2 · min−1) were significantly lower after metformin as compared with the placebo-treated group (P < 0.001).

CONCLUSIONS

Metformin treatment was associated with significantly lower day-long plasma glucose and FFA concentrations. Although overnight hepatic glucose production was unchanged following treatment with metformin, the overnight glucose metabolic clearance rate significantly increased. Given these findings, it is suggested that at least part of the antihyperglycemic effect of metformin is due to an increase in glucose uptake, secondary to a decrease in release of FFA from adipose tissue, and lower circulating FFA concentrations.
Ambulatory Medical Care for Non-Hispanic Whites, African-Americans, and Mexican-Americans With NIDDM in the U.S
Authors: Cowie Catherine C , Harris Maureen I
Published: March 2007

OBJECTIVE

To assess whether medical care for diabetes is different among non-Hispanic whites, African-Americans, and Mexican-Americans with NIDDM.

RESEARCH DESIGN AND METHODS

A questionnaire was administered to a representative U.S. sample of 2,170 noninstitutionalized adults with NIDDM. Information was obtained on physician visits, hyperglycemic therapy, monitoring of glycemic control, screening for and monitoring of complications, and diabetes education.

RESULTS

About 90% of subjects had a regular diabetes physician, and the physician visit rate was similar by race (median of four visits per year). African-Americans were more likely to be treated with insulin (51.9%) than non-Hispanic whites (35.9%, P < 0.0001) and Mexican-Americans (46.2%). Among insulin-treated subjects, African-Americans were less likely to use multiple daily insulin injections (35.1 vs. 53.8% of non-Hispanic whites [P < 0.0001] and 50.5% of Mexican-Americans [P = 0.027]) and were less likely to self-monitor their blood glucose at least once per day (14.0 vs. 29.8% of non-Hispanic whites [P < 0.0001] and 29.0% of Mexican-Americans). The rates of visits to specialists for diabetes complications, physician testing of blood glucose, and screening for hypertension, retinopathy, and foot problems were not substantially different among the three race/ethnic groups. A higher proportion of African-Americans (43.3%) than non-Hispanic whites (31.5%, P < 0.0001) and Mexican-Americans (25.6%, P = 0.001) had received patient education; however, the median number of hours of instruction was lower for African-Americans.

CONCLUSIONS

The frequency of diabetes care is similar among non-Hispanic whites, African-Americans, and Mexican-Americans. The major differences relate to methods of glycemic control and patient education.
Phobic Symptoms, Particularly the Fear of Blood and Injury, Are Associated With Poor Glycemic Control in Type I Diabetic Adults
Authors: Berlin Ivan , Bisserbe Jean Claude , Eiber Renate , Balssa Nicolas , Sachon Claude , Bosquet Frédéric , Grimaldi André
Published: March 2007

OBJECTIVE

To investigate the presence of psychiatric disorders and symptoms in type I diabetic patients and to identify those that may influence metabolic control as assessed by GHb levels.

RESEARCH DESIGN AND METHODS

This was a cross-sectional study. One hundred and two consecutive patients with type I diabetes who were regular outpatient visitors of a diabetology department were evaluated. The psychiatric assessments included self-rating questionnaires (General Health Questionnaire and Fear Questionnaire) and observer-rating questionnaires (Montgomery-Asberg Depression Rating Scale [MADRS] and Mini International Interview). Diabetic characteristics were assessed by a structured interview. The observer was blind to the diabetic characteristics of the patients.

RESULTS

Type I diabetic patients with GHb levels ≥ 8% had higher psychological distress, scored significantly higher for symptoms of agoraphobia and for fear of blood and injury, had substantially higher levels of anxiety-depression, and performed significantly fewer blood glucose measurements per day. They did not differ in MADRS score from patients with GHb levels < 8%. Multivariate analysis showed that GHb was positively associated with the total score of phobic symptoms and the level of anxiety-depression and inversely associated with the number of daily blood glucose measurements. These factors explained 41% of the variance of GHb. The inverse relationship between GHb and the number of blood glucose measurements per day was mainly influenced by the fear of blood and injury. Patients with high scores for the fear of blood and injury performed fewer blood glucose measurements and had poorer glycemic control; conversely, subjects without fear of blood and injury performed more daily blood glucose measurements and had better glycemic control.

CONCLUSIONS

Phobic symptoms are frequent in patients with type I diabetes. The intensity of phobic symptoms and anxiety-depression negatively influences metabolic control. Increased fear of blood and injury may lead some patients to perform few home blood glucose measurements and may result in poorer glycemic control. This suggests that, by decreasing the fear of blood, injury, and injection, metabolic control may be improved.
A Cross-Sectional Study Comparing Two Quantitative Sensory Testing Devices in Individuals With Diabetes
Authors: Maser Raelene E , Laudadio Charles , Lenhard M James , DeCherney G Stephen
Published: March 2007

OBJECTIVE

This study was designed to compare circumference discrimination thresholds, as assessed by the Tacticon (Tacticon, Inc., Westtown, PA), a new quantitative sensory testing (QST) device, with vibratory thresholds, an assessment modality of large sensory nerve fibers, in individuals with diabetes.

RESEARCH DESIGN AND METHODS

In this study, 150 individuals with diabetes were evaluated. Vibratory thresholds and circumference discrimination thresholds, evaluated with the Tacticon, were determined using a two-alternative forced-choice procedure.

RESULTS

Vibratory thresholds increased with decreasing ability to discriminate differences in circumference (P < 0.001) for those below and above 50 years of age. Agreement between the two QST devices was assessed via the kappa-statistic in both age-groups (i.e., ≤ 50 years old [kappa = 0.67], > 50 years old [κ = 0.55]). In multiple logistic regression, where circumference discrimination thresholds were the dependent variable, age, duration of diabetes, and height were found to be independently associated for those > 50 years old.

CONCLUSIONS

The Tacticon offers a simple method of assessing the complex function of area discrimination. Our results suggest that the Tacticon can detect neuropathy in the primary care setting. Its cost, portability, and ease of use provide some advantages over existing QST equipment.
Impaired Glucose Tolerance is Normalized by Treatment With the Thiazolidinedione Troglitazone
Authors: Antonucci Tammy , Whitcomb Randall , McLain Richard , Lockwood Dean
Published: March 2007

OBJECTIVE

The primary purpose of this study was to assess the effects of 12 weeks of treatment with either troglitazone, an investigational thiazolidinedione that acts as an insulin-action enhancer, or placebo in patients with impaired glucose tolerance (IGT).

RESEARCH DESIGN AND METHODS

A total of 51 subjects with IGT between 24 and 77 years of age were enrolled in this multicenter, double-blind, placebo-controlled, parallel group study (troglitazone, 25 patients; placebo, 26 patients). Patients were randomly assigned to receive either 400 mg troglitazone (every morning [QAM]) or placebo (QAM). The main outcome measure was the oral glucose tolerance test (OGTT) assessing glucose, insulin, and C-peptide levels in the fasting state and every 30 min up to 2 h after ingesting the glucose load. Fasting serum levels of HbA1c, fructosamine, lipids, and blood pressure were also measured.

RESULTS

A total of 46 patients completed the study. The glucose, insulin, and C-peptide responses after a glucose load were significantly reduced at 6 and 12 weeks in the troglitazone treatment group. After 6 weeks of treatment, 75% (n = 18) of those taking troglitazone had improved to normal glucose tolerance, whereas only 38% (n = 9) of those of placebo showed improvement (P = 0.008). After 12 weeks of treatment, 80% (n = 16) of the troglitazone treatment group had normalized their glucose tolerance, while only 48% (n = 10) of those on placebo had converted to normal (P = 0.016). Fasting triglyceride levels in the troglitazone treatment group had decreased by 40 mg/dl (0.45 mmol/l) (P = 0.0016). Other lipid measurements, blood pressure, glycosylated hemoglobin, and fructosamine were normal at baseline for both treatment groups and remained normal throughout the study.

CONCLUSIONS

The glycemic response after a glucose load is statistically and clinically significantly improved for patients with IGT treated with troglitazone.
Effect of Intensive Treatment of Diabetes on the Risk of Death or Renal Failure in NIDDM and IDDM
Authors: Hellman Richard , Regan Julie , Rosen Howard
Published: March 2007

OBJECTIVE

To examine the effectiveness and safety of long-term intensive therapy in NIDDM and IDDM.

RESEARCH DESIGN AND METHODS

In a private practice setting with a multi-disciplinary team, we compared the rates of total mortality, cardiac-specific mortality, and severe renal failure over 14 years in a cohort of 780 eligible patients, 209 patients with a longer duration of intensive therapy (median duration > 11 years, group I) and 571 patients with shorter duration of intensive therapy (median duration < 1 year, group II). A comorbidity index was used to assess the degree of prognostic risk at baseline. A comprehensive diabetes program was the therapeutic intervention. The endocrinologists and diabetes care team provided primary care, aggressive cardiovascular screening, and risk reduction. Intensive insulin therapy was used in 95.7% of group I IDDM and 66.0% of group I NIDDM patients.

RESULTS

The overall median HbA1c for group I was 7.3%. Compared with group II, the overall reduction in cumulative total mortality in group I was 22%. In the cohort with less severe initial comorbidity, the reduction in total mortality was 45%. We found similar reductions in renal failure rates in IDDM and in cardiac mortality in NIDDM patients on intensive insulin therapy.

CONCLUSIONS

This comprehensive diabetes program is associated with lowered mortality and morbidity in both IDDM and NIDDM. Intensive insulin therapy in long-term patients with NIDDM does not increase cardiac mortality. Intensive therapy is safe and effective in NIDDM within the context of a comprehensive program.
NIDDM Patients' Fears and Hopes About Insulin Therapy: The basis of patient reluctance
Authors: Hunt Linda M , Valenzuela Miguel A , Pugh Jacqueline A
Published: March 2007

OBJECTIVE

This study examines NIDDM patients' attitudes toward insulin injections, the basis of these attitudes, and how they may affect patients' willingness to take insulin.

RESEARCH DESIGN AND METHODS

Forty-four low-income Mexican American NIDDM patients were interviewed using open-ended in-depth interviewing techniques. Transcripts were analyzed using techniques of content analysis. Data classification was cross-checked in analysis conferences and through a second researcher coding 50% of the cases, comparing the results, then resolving any discrepancies.

RESULTS

Patients' positive attitudes toward insulin focus on its efficacy and efficiency, the avoidance of complications, and feeling better and more energetic. Negative attitudes were much more frequently discussed and include “technical concerns”: anxiety about the pain, proper techniques, and general hassles of taking injections; about hypoglycemic symptoms; and about insulin causing serious health problems; and “experimental concerns”: sensing that the disease has progressed into a serious phase, that past treatment efforts have failed, and that the patient has not taken proper care. Attitudes were based on personal experience, observation, what others say, and interactions with health care professionals.

CONCLUSIONS

Results from the few published reports on NIDDM patients' attitudes about insulin from various cultural settings were consistent with our findings, indicating that these themes may be generally applicable to a wider population. It is recommended that health care providers take care to avoid unwitting promotion of negative attitudes toward insulin and actively elicit and respond to patient attitudes to reduce reluctance to take the medication.
High Variability of Glycated Hemoglobin Concentrations in Patients With IDDM Followed Over 9 years: What is the best index of long-term glycemic control?
Authors: Singh Baldev M , McNamara Catherine , Wise Peter H
Published: March 2007

OBJECTIVE

To determine variability of long-term glycemic control in patients with IDDM.

RESEARCH DESIGN AND METHODS

A retrospective analysis of HbA1 among 122 IDDM patients followed over 9 years.

RESULTS

Annual group mean HbA1 ranged from 8.4 to 9.3% with large standard deviations (1.7–2.0%), indicating marked variability among individuals. Fluctuations of more than ± 1% HbA1 occurred in 50% of the patients year to year, and over 9 years the minimum-maximum range was > 3 and > 5% HbA1 in 55 and 11% of patients, respectively. In any one year, 22–43% of patients had HbA1 < 8%, but over 9 years only 3.3% were consistently < 8%. Groups divided according to baseline HbA1 of < 8, 8–10, and > 10% were significantly separated over 9 years by frequency distribution analysis of individual mean HbA1 but were indistinguishable when analyzed by individual HbA1 interquartile range (measure of variability).

CONCLUSIONS

High variability of long-term glycemic control is a marked feature of IDDM, the extent of which may be relevant to microvascular risk.
Prevalence of NIDDM Among Populations of the African Diaspora
Authors: Cooper Richard S , Rotimi Charles N , Kaufman Jay S , Owoaje Eme E , Fraser Henry , Forrester Terrence , Wilks Rainford , Riste Lisa K , Cruickshank J Kennedy
Published: March 2007

OBJECTIVE

Rates of non-insulin-dependent diabetes mellitus have risen sharply in recent years among blacks in the U.S. and the U.K. Increases in risk have likewise been observed in the island nations of the Caribbean and in urban West Africa. To date, however, no systematic comparison of the geographic variation of NIDDM among black populations has been undertaken.

RESEARCH DESIGN AND METHODS

In the course of an international collaborative study on cardiovascular disease, we used a standardized protocol to determine the rates of NIDDM and associated risk factors in populations of the African diaspora. Representative samples were drawn from sites in Nigeria, St. Lucia, Barbados, Jamaica, the United States, and the United Kingdom. A total of 4,823 individuals aged 25–74 years were recruited, all sites combined.

RESULTS

In sharp contrast to a prevalence of 2% in Nigeria, age-adjusted prevalences of self-reported NIDDM were 9% in the Caribbean and 11% in the U.S. and the U.K. Mean BMI ranged from 22 kg/m2 among men in West Africa to 31 kg/m2 in women in the U.S. Disease prevalence across sites was essentially collinear with obesity, pointing to site differences in the balance between energy intake and expenditure as the primary determinant of differential NIDDM risk among these populations.

CONCLUSIONS

In ethnic groups sharing a common genetic ancestry, these comparative data demonstrate the determining influence of changes in living conditions on the population risk of NIDDM.
Mobilization of Visceral Adipose Tissue Related to the Improvement in Insulin Sensitivity in Response to Physical Training in NIDDM: Effects of branched-chain amino acid supplements
Authors: Mourier Agnès , Gautier Jean-François , Kerviler Eric De , Bigard André Xavier , Villette Jean-Marie , Garnier Jean-Pierre , Duvallet Alain , Guezennec Charles Yannick , Cathelineau Gérard
Published: March 2007

OBJECTIVE

To evaluate the effects of an intense physical training program on abdominal fat distribution, glycemic control, and insulin sensitivity in patients with NIDDM and to determine whether branched-chain amino acid (BCAA) supplements influence these effects.

RESEARCH DESIGN AND METHODS

Twenty-four patients (ages 45 ± 2 [mean ± SE] years, BMI 30.2 ± 0.9 kg/m2, HbA1c 7.9 ± 0.3%) were randomly assigned to four groups: training plus BCAA supplement (n = 6), training plus placebo (n = 6), sedentary plus BCAA supplement (n = 6), and sedentary plus placebo (n = 6). Physical training consisted of a supervised 45-min cycling exercise at 75% of their oxygen uptake peak (VO2 peak) two times per week and an intermittent exercise one time per week for 2 months.

RESULTS

Patients who exercised increased their VO2 peak by 41% and their insulin sensitivity by 46%. Physical training significantly decreased abdominal fat evaluated by magnetic resonance imaging (umbilicus), with a greater loss of visceral adipose tissue (VAT) (48%) in comparison with the loss of subcutaneous adipose tissue (18%), but did not significantly affect body weight. The change in visceral abdominal fat was associated with the improvement in insulin sensitivity (r = 0.84, P = 0.001). BCAA supplementation had no effect on abdominal fat and glucose metabolism.

CONCLUSIONS

Physical training resulted in an improvement in insulin sensitivity with concomitant loss of VAT and should be included in the treatment program for patients with NIDDM.
Prevalence and Determinants of Solid and Liquid Gastric Emptying in Unstable Type I Diabetes: Relationship to postprandial blood glucose concentrations
Authors: Lyrenås Ebbe B , Olsson Eva H K , Arvidsson Ulla C , Örn Thomas J , Spjuth Jan H
Published: March 2007

OBJECTIVE

To compare postprandial blood glucose levels with gastric emptying (GE) time after intake of a solid and a nutrient liquid meal in patients with unstable, type I diabetes.

RESEARCH DESIGN AND METHODS

The subjects studied were 15 patients with long-standing type I diabetes who during the last year repeatedly reported unexplained episodes of instability in their blood glucose regulation, including postprandial hypoglycemia. All patients were on a meal-administered, fast-acting insulin regimen. As control group, 19 healthy subjects were studied. GE was measured at two separate occasions, using a gamma camera after intake of either a solid or a nutrient liquid, isotope-labeled meal. Measurement of GE was done directly after meal completion and at 30-min intervals for 2 h. Insulin was taken 30 min before intake of the meal. Blood glucose was measured 30 min before the meal, after meal completion and at 30, 60, 90, and 120 min after start of the meal. All patients were evaluated for evidence of autonomic neuropathy and were asked for signs of gastrointestinal motor dysfunction.

RESULTS

Seven (44%) of the patients had significantly delayed emptying of the solid meal (three men, four women) (P < 0.01), of whom one woman also had delayed emptying of the liquid meal compared with the healthy control subjects. Changes in blood glucose concentration were correlated to GE time with, in the group with delayed GE, a significant fall after the solid meal compared with the liquid meal (P < 0.05). The lag phase was prolonged in the women compared with the men, reaching significance in the patient group (P < 0.01). The women, patients as well as control subjects, had throughout the study a prolonged emptying time compared with the men after both the solid and the liquid meal. No correlation between GE and blood glucose concentration could be found.

CONCLUSIONS

Delayed GE of a solid meal is commonly found in patients with type I diabetes and may be one cause of unstable blood glucose regulation. Women, patients as well as control subjects, seem to have a more prolonged GE than men. Awareness of gastric function in patients with type I diabetes is essential, especially in patients treated with meal-administered, fast-acting insulin.
Slow Gastric Emptying in Type I Diabetes: Relation to Autonomic and Peripheral Neuropathy, Blood Glucose, and Glycemic Control
Authors: Merio René , Festa Andreas , Bergmann Helmar , Eder Thomas , Eibl Nicole , Stacher-Janotta Giselheld , Weber Ute , Budka Christine , Heckenberg Andrea , Bauer Peter , Francesconi Mario , Schernthaner Guntram , Stacher Georg
Published: March 2007

OBJECTIVE

To investigate whether autonomic neuropathy or hyperglycemia plays a crucial etiological role in gastric retention of ingesta frequently found in type I diabetic patients.

RESEARCH DESIGN AND METHODS

We investigated the gastric emptying of a radiolabeled semisolid 1,168 kJ meal in 38 female and 45 male patients (age 18–75 years; illness duration 3–46 years). None took drugs affecting gastrointestinal motility. Fasted patients underwent tests of cardiovascular autonomic and peripheral nerve function. Blood glucose levels were determined before and after the scintigraphic recording of gastric emptying.

RESULTS

The percentage of meal remaining in the stomach at the end of the 50-min recording time was related significantly to the patients' degree of cardiovascular autonomic neuropathy [r (81) = 0.235, P < 0.028] but not to their degree of peripheral neuropathy, preprandial blood glucose level, HbA1c indicative of glycemic control, diabetes duration, and age. The patients' mean residual percentage of meal was significantly > that of 48 healthy subjects, that is, 71.1 ± 15.1 vs. 53.5 ± 13.1% [means ± SD; t (129) = 6.48, P < 0.0001]. The healthy individuals' mean residual percentage + 2 SD was exceeded in 22 patients.

CONCLUSIONS

Slow gastric emptying in patients with type I diabetes seems related to the degree of autonomic neuropathy but not to peripheral neuropathy, actual blood glucose, and glycemic control.
Activated Protein C Resistance in Type I Diabetes
Authors: Gruden Gabriella , Olivetti Carla , Cavallo-Perin Paolo , Bazzan Mario , Stella Stefania , Tamponi Giacomo , Pagano Gianfranco
Published: March 2007

OBJECTIVE

To compare activated protein C (aPC) sensitivity in 37 type I diabetic patients and 33 healthy control subjects.

RESEARCH DESIGN AND METHODS

In this study, 37 type I diabetic patients and 33 healthy control subjects without personal or familial history of venous thrombosis and coagulation disorders, infections, intercurrent conditions, serum lupus anticoagulant, clinical cardiovascular complications, or drugs were examined.

RESULTS

The aPC ratio (aPTT [activated partial thromboplastin time] with and without aPC) was significantly lower in the type I diabetic patients than in the control subjects (P = 0.005).

CONCLUSIONS

These results suggest that the final steps of the protein C/S inhibiting system could be abnormal in type I diabetes.
Elevated Ambulatory Blood Pressure in Microalbuminuric IDDM Patients Is Inversely Associated With Renal Plasma Flow: A compensatory mechanism?
Authors: Poulsen P L , Juhl B , Ebbehøj E , Klein F , Christiansen C , Mogensen C E
Published: March 2007

OBJECTIVE

To evaluate the relationship between renal function, ambulatory blood pressure (AMBP), and glycemic control in microalbuminuric IDDM patients compared with normoalbuminuric patients.

RESEARCH DESIGN AND METHODS

Nineteen male patients (age 33 ± 6 years) with slight microalbuminuria (UAE 20–70 μg/min) were compared with 19 normoalbuminuric (UAE < 15 μg/min) age-matched (33 ± 6 years) male patients. Through constant infusion technique, 125I-iothalamate marked the glomerular filtration rate (GFR), and 131I-hippuran marked effective renal plasma flow (RPF). AMBP was measured by oscillometric technique (Spacelabs 90202).

RESULTS

The microalbuminuric group had higher daytime systolic AMBP (132 ± 11 vs. 125 ± 7 mmHg, P < 0.05) and a poorer glycemic control (HbA1c 9.5 ± 1.5 vs. 8.2 ± 1.3%, P < 0.01). GFR (135 ± 22 and 135 ± 17 ml/min) and RPF (598 ± 112 and 542 ± 98 ml/min) were similar in the two groups. In the microalbuminuric group, daytime systolic AMBP was inversely correlated to both RPF (r = −0.77, P < 0.005) and GFR (r = −0.53, P = 0.02). HbA1c and GFR correlated positively in the microalbuminuric group (r = 0.47, P < 0.04). In contrast, the normoalbuminuric patients exhibited no such associations.

CONCLUSIONS

IDDM patients with moderate microalbuminuria have elevated AMBP and a strong negative association between AMBP and RPF. This leaves several possibilities of interpretation. Primary blood pressure increase (of unknown origin) may induce morphological changes leading to reduction in renal function. Alternatively, blood pressure increase early in the course of incipient nephropathy may represent a compensatory mechanism, initially aiming at preservation of renal function, but later becoming maladaptive.
Distinct Genetic and Immunological Features in Patients With Onset of IDDM Before and After Age 40
Authors: Lohmann Tobias , Sessler Jochen , Verlohren Hans-Joachim , Schröder Sabine , Rötger Julia , Dãhn Karsten , Morgenthaler Nils , Scherbaum Werner A
Published: March 2007

OBJECTIVE

Young age at onset is a relevant parameter associated with a rapid progression of IDDM. Our major aim was to define differences between IDDM patients with age at diagnosis > 40 years and adult IDDM with onset at a younger age.

RESEARCH DESIGN AND METHODS

The correlation between islet-related antibodies (islet cell antibodies [ICAs] and antibodies [Abs] to GAD and the tyrosine phosphatase IA2), T-cell responses to GAD peptides and HLA class II isotypes was investigated in 23 IDDM patients 12–38 years of age at onset (group 1), 24 patients with IDDM > 40 years of age at onset (group 2), and 12 healthy control subjects. ICAs were measured by indirect immunofluorescence, and GAD-Ab and IA2-Ab were measured by immunoprecipitation tests. T-cell responses against GAD peptides, which had been identified as typical for IDDM, were tested by 5-day proliferation assays. HLA class II alleles were typed by polymerase chain reaction.

RESULTS

ICAs and GAD-Abs were more prevalent in IDDM patients than in control subjects (P < 0.001), but only IDDM group 1 had IA2-Abs (P < 0.001 compared with IDDM group 2 and control subjects). Moreover, antibody combinations differed between IDDM patients of groups 1 and 2. T-cell responses to GAD peptides were seen in 67% of IDDM group 1 and in 71% of IDDM group 2 (P < 0.02 compared with control subjects). IDDM patients of group 1 were more frequently DR4+/DQ8+ and less frequently DR2+/DQ0602+ compared with IDDM patients of group 2 (P < 0.05).

CONCLUSIONS

Our data provide strong evidence for humoral and cellular autoimmunity in adult IDDM patients with onset both before and after 40 years of age. However, late-onset differs from young-onset IDDM with respect to Ab profiles, especially a lack of IA2-Ab, and HLA class II types. These findings have consequences for the diagnostic strategy for identifying slow-onset IDDM in individuals after 40 years of age.
Diabetes Self-Management: Self-reported recommendations and patterns in a large population
Authors: Ruggiero Laurie , Glasgow Russell , Dryfoos Janet M , Rossi Joseph S , Prochaska James O , Orleans C Tracy , Prokhorov Alexander V , Rossi Susan R , Greene Geoffrey W , Reed Gabrielle R , Kelly Kim , Chobanian Lisa , Johnson Suzann
Published: March 2007

OBJECTIVE

Diabetes self-management is the cornerstone of overall diabetes management. Yet many questions concerning self-management remain unanswered. The current study was designed to examine several questions about diabetes self-management: 1) What do individuals report being told to do? 2) What are their self-reported levels and patterns of self-care? 3) Are there differences on self-reported self-management recommendations and levels across various subgroups?

RESEARCH DESIGN AND METHODS

Mailed surveys were returned by 2,056 individuals (73.4% response rate). Of the total, 13.8% had IDDM and the remainder had NIDDM, with 65% of the NIDDM group using insulin.

RESULTS

The levels and patterns of self-management were consistent with those found in previous studies, i.e., individuals most regularly followed their prescribed medication regimen and least regularly followed recommendations for lifestyle changes of diet and exercise. There were significant differences on reported self-management recommendations across different subgroups. Comparisons on level of self-management across diabetes type revealed significant differences for diet and glucose testing. Differences were also found on self-management levels for a number of individual characteristics, including age, working status, and type of insurance, along with knowledge of the Diabetes Control and Complications Trial findings.

CONCLUSIONS

These findings provide important information on perceived self-management recommendations and the specific self-management levels and patterns in individuals with diabetes. The current findings may help health professionals better understand the levels and correlates of diabetes self-management and direct future research.
Health Insurance and the Financial Impact of IDDM in Families With a Child With IDDM
Authors: Songer Thomas J , LaPorte Ronald E , Lave Judith R , Dorman Janice S , Becker Dorothy J
Published: March 2007

OBJECTIVE

To examine the health insurance experience and out-of-pocket health care costs of families with a child with IDDM.

RESEARCH DESIGN AND METHODS

A case-control study of 197 families with a child with IDDM and 142 control families with no diabetic children was conducted. IDDM-affected families were identified from the Allegheny County IDDM Registry. Brothers and sisters of the parents in the IDDM-affected families were asked to participate as control subjects. Health insurance coverage and the money that families spent on health care services and supplies not reimbursed by insurance (out-of-pocket costs) were assessed by questionnaire.

RESULTS

No difference was found between the IDDM-affected and control families in the percentages with or without insurance. Families with low household incomes ($10,000–$19,999) were at the greatest risk for having no insurance. While coverage provided by private plans was similar between the IDDM-affected and control families, many families had no reimbursement for insulin (10%), syringes (10%), or blood testing strips (30%). Out-of-pocket expenses were 56% higher in the IDDM-affected families than in the control families. Seventeen percent of the IDDM-affected families had expenses over 10% of their household income. This particularly affected families with low household incomes. Pre-existing illness clauses and insurance denial affected only a small proportion of the case families.

CONCLUSIONS

These data illustrate that most families with a child with IDDM have health insurance, yet still incur larger out-of-pocket health care costs than do families without the presence of diabetes. IDDM-affected families likely face a number of economic decisions regarding health insurance and the use of health care.
Model of Complications of NIDDM: I. Model construction and assumptions
Authors: Eastman Richard C , Javitt Jonathan C , Herman William H , Dasbach Erik J , Zbrozek Arthur S , Dong Fred , Manninen Diane , Garfield Sanford A , Copley-Merriman Catherine , Maier William , Eastman Jeffery F , Kotsanos James , Cowie Catherine C , Harris Maureen
Published: March 2007

OBJECTIVE

To develop a model of NIDDM for analyzing prevention strategies for NIDDM.

RESEARCH DESIGN AND METHODS

A Markov type model with Monte Carlo techniques was used. Age, sex, and ethnicity of cohort was based on U.S. data. Incidence rates of complications were also based on community and population studies.

RESULTS

Nonproliferative retinopathy, proliferative retinopathy, and macular edema are predicted in 79, 19, and 52%, respectively, of people with NIDDM; 19% are predicted to develop legal blindness. Microalbuminuria, gross proteinuria, and end-stage renal disease related to diabetes are predicted in 53, 40, and 17%, respectively. Symptomatic sensorimotor neuropathy and lower-extremity amputation are predicted in 31 and 17%, respectively. Cardiovascular disease is predicted in 39%. Higher rates of complications (1.1−3.0×) are predicted in minority populations. Predicted average life expectancy is 17 years after diagnosis.

CONCLUSIONS

A probabilistic model of NIDDM predicts the vascular complications of NIDDM in a cohort representative of the incident cases of diabetes in the U.S. before age 75 years. Predictions of complications and mortality are consistent with the known epidemiology of NIDDM. The model is suitable for evaluating the effect of preventive interventions on the natural history of NIDDM.
Bacille Calmette-Guérin Vaccination and Incidence of IDDM in Montreal, Canada
Authors: Parent Marie-Élise , Siemiatycki Jack , Menzies Richard , Fritschi Lin , Colle Eleanor
Published: March 2007

OBJECTIVE

To describe the association between Bacille Calmette-Guérin (BCG) vaccination and IDDM development in two different case-control series (A and B) in Montreal.

RESEARCH DESIGN AND METHODS

Case-control series A comprised 93 IDDM cases and 2,903 control subjects who participated in a community-based tuberculin reactivity survey and who belonged to the same birth cohorts and areas of residence as the IDDM cases, Case-control series B comprised 249 IDDM cases and 431 age- and sex-matched friends and neighborhood control subjects.

RESULTS

In series A, the BCG vaccination prevalence among cases and control subjects was 21.5% (95% CI 13.2–29.8%) and 22.3% (95% CI 20.8–23.8%), respectively. The odds ratio (OR) for IDDM associated with BCG vaccination was 1.09 (95% CI 0.62–1.91), after adjusting for the birth cohorts and areas of residence. The vaccination prevalence in series B was 17.7% (95% CI 13.0–22.4%) among cases and 15.1% (95% CI 11.7–18.5%) among control subjects. The OR for IDDM due to BCG vaccination was 1.26 (95% CI 0.79–2.02), taking into account the matched sets. Only one case (3.3%) from series B who had been vaccinated at birth was diagnosed by age 5, compared with 52 cases (24.5%) who had not been vaccinated (P < 0.01).

CONCLUSIONS

The lower proportion of birth-vaccinated IDDM cases diagnosed at a very young age, compared with nonvaccinated cases, possibly reflects a temporary boost of the immune functions after vaccination. However, as a whole, results from these analyses fail to support a protective role of BCG vaccination against juvenile-onset IDDM.
Glycosaminoglycans Delay the Progression of Nephropathy in NIDDM
Authors: Solini Anna , Vergnani Luciana , Ricci Franco , Crepaldi Gaetano
Published: March 2007

OBJECTIVE

To determine the effect of oral administration of glycosaminoglycans on metabolic control and albumin excretion rate (AER) in NIDDM patients with increased urinary albumin excretion.

RESEARCH DESIGN AND METHODS

Twelve NIDDM hypertensive patients (age 52 ± 3 years, HbA1c 7.7 ± 0.2%) on antihypertensive treatment were enrolled in a double-blind placebo-controlled study, assuming either placebo or sulodexide (100 mg/day) for 4 months; at the end of this period, a crossover was performed. We have evaluated routine biochemical parameters plus AER and coagulative function every 2 months.

RESULTS

Both plasma fibrinogen (from 4.15 ± 0.32 to 2.77 ± 0.47 mmol/l) and AER (from 128.3 ± 40.6 to 39.6 ± 11.9 μg/min) decreased significantly after treatment with glycosaminoglycans in respect to placebo; moreover, blood pressure control ameliorated, also in the absence of any variation of therapy.

CONCLUSIONS

Glycosaminoglycan therapy, likely in association with a satisfactory control of blood pressure values, seems to prevent the progression of diabetic nephropathy in NIDDM.
Cochlear Dysfunction in IDDM Patients With Subclinical Peripheral Neuropathy
Authors: Leo Mauro A S Di , Nardo Walter Di , Cercone Stefania , Ciervo Amedeo , Monaco Mauro Lo , Greco Aldo V , Paludetti Gaetano , Ghirlanda Giovanni
Published: March 2007

OBJECTIVE

To investigate the function of the auditory pathway from the cochlea to the auditory cortex in subjects with IDDM.

RESEARCH DESIGN AND METHODS

Brain stem, middle-, and long-latency auditory-evoked responses and evoked otoacoustic emissions were measured in 48 normally hearing IDDM patients and in age- and sex-matched nondiabetic subjects. Peripheral neuropathy was diagnosed by nerve conduction velocity (NCV) at the peroneal and sural nerves. Auditory brain stem responses (ABRs) reflect auditory pathway function within the brain stem; middle-latency responses (MLRs) and long-latency responses (LLRs) originate from the auditory cortex; and evoked otoacoustic emissions (EOAEs) give objective information about preneural, mechanical elements of the cochlear function.

RESULTS

A subclinical peripheral neuropathy was found in 12 diabetic patients. We found higher latencies of waves I (t = 4.4, P < 0.0001), III (t = 3.7, P = 0.0004), and V (t = 2.7, P = 0.008) of ABRs in diabetic patients (I: 1.7 ± 0.13 ms; III: 3.9 ± 0.17 ms; V: 5.7 ± 0.24 ms), compared with those of the control group (I: 1.6 ± 0.13 ms; III: 3.7 ± 0.18 ms; V: 5.6 ± 0.17 ms). However, neither central transmission time (i.e., the wave interpeak I-V) nor MLRs and LLRs were found to be significantly different in diabetic and control subjects. Mean EOAE amplitude was found to be significantly reduced (F = 4.2, P = 0.02) in diabetic patients with a reduced NCV (7.6 ± 3.9 dB; Scheffé test: P = 0.03), but not in those without neuropathy (9.1 ± 4.2 dB), compared with the control group (10.8 ± 3.1 dB). No correlations were found between duration of diabetes and EOAEs or between sural NCV and peroneal NCV and metabolic control. EOAEs were not correlated with peroneal and sural NCVs.

CONCLUSIONS

Our results indicate that the early preneural dysfunction of cochlear receptors causes a prolonged activation of the peripheral portion of the auditory pathway, while signal conduction along the central auditory pathway was shown to be normal in diabetes.
Incomplete Elimination of the ABBOS Epitope of Bovine Serum Albumin Under Simulated Gastrointestinal Conditions of Infants
Authors: Alting Arno C , Meijer Ron J G M , van Beresteijn Emerentia C H
Published: March 2007

OBJECTIVE

Because the bovine serum albumin residues 126–144 (ABBOS) have been reported to be responsible for the autoimmune reaction directed against pancreatic islet cells, it was our aim to study the potential survival of the ABBOS epitope during digestion in the gastrointestinal tract.

RESEARCH DESIGN AND METHODS

Either nontreated (commercially available) or heat-treated bovine serum albumin (BSA) was hydrolyzed in vitro with pepsin at a pH of 2.0, 3.0, and 4.0 and subsequently with pancreatic enzymes at a pH of 7.5. Cross-reactivity between the ABBOS peptide and the BSA hydrolysates was determined by competitive enzyme-linked immunosorbent assay (ELISA) using a rabbit polyclonal antibody raised against the ABBOS peptide in BSA.

RESULTS

Biochemical findings clearly showed that the degradation of BSA during simulated physiological digestion depended on its conformation and on the pH of its pepsin-catalyzed hydrolysis. Raising the pH of the pepsin-catalyzed hydrolysis from 2.0 to 4.0 decreased the efficiency of the process, especially when BSA had first been denatured by heat treatment. As a consequence, a large proportion of the cross-reactive anti-ABBOS antibody-binding sites was still intact in the final hydrolysates.

CONCLUSIONS

The present results suggest that the ABBOS epitope of BSA will not be completely eliminated during digestion under conditions that prevail in the stomach of infants (pH 3–4).
Gestational Diabetes Is a Herald of NIDDM in Navajo Women: High rate of abnormal glucose tolerance after GDM
Authors: Steinhart Jonathan R , Sugarman Jonathan R , Connell Fred A
Published: March 2007

OBJECTIVE

To estimate the rate of deterioration of glucose tolerance and evaluate risk factors for development of NIDDM in Navajo women with a history of gestational diabetes mellitus (GDM).

RESEARCH DESIGN AND METHODS

A retrospective analysis of 111 GDM deliveries over a 4-year period, 1983–1987, was conducted in 1994 to determine glucose tolerance status. Patients who had not developed NIDDM were recalled for a 2-h glucose tolerance test (GTT). Tested and non-tested patients were compared, as estimate of conversion to NIDDM was calculated, and risk factors for NIDDM were evaluated. A life-table analysis was developed to estimate the probability of NIDDM after GDM.

RESULTS

At the time of chart review, 32 patients (29%) had already been diagnosed with NIDDM. Of the patients, 79 were offered GTT testing, and 56 (71%) returned for follow-up; 15 were diagnosed with NIDDM and 17 with impaired glucose tolerance (IGT); 47 (42%) and 64 (58%) patients in the cohort had developed NIDDM or NIDDM/IGT at the conclusion of the study period. Patients who developed NIDDM had greater BMIs, parity, and infant weights. Fasting blood glucose > 5.83 mmol/l, GTT > 41.63 mmol/l, and recurrence of GDM were associated with later NIDDM. A life-table analysis estimated a 53% likelihood of having NIDDM at an 11-year follow-up; a second model, based only on patients with known NIDDM status, predicted a 70% rate of NIDDM at an 11-year follow-up.

CONCLUSIONS

A high proportion of Navajo women with GDM progressed to NIDDM. Postpartum counseling and periodic GTTs are recommended.
Health-Related Quality-of-Life Results From Multinational Clinical Trials of Insulin Lispro: Assessing benefits of a new diabetes therapy
Authors: Kotsanos James G , Vignati Louis , Huster William , Andrejasich Carol , Boggs Mary Beth , Jacobson Alan M , Marrero David , Mathias Susan D , Patrick Donald , Zalani Sunita , Anderson James
Published: March 2007

OBJECTIVE

To compare health-related quality of life (HRQOL) in patients with diabetes receiving insulin lispro with patients receiving regular human insulin (Humulin R).

RESEARCH DESIGN AND METHODS

We performed two randomized comparative studies over a 6-month period (3 months per treatment). Primary analyses used crossover baseline to 3-month changes in HRQOL scores. Ninety-three principal investigators in Canada, France, Germany, and the U.S. participated in these studies. One HRQOL crossover study included 468 patients with type I diabetes; the other HRQOL crossover study included 474 patients with type II diabetes. In both studies, patients were taking insulin at least 2 months before enrollment. Primary outcomes included two generic HRQOL domains, energy/fatigue and health distress, and two diabetes-specific domains, treatment satisfaction and treatment flexibility. Thirty secondary outcomes included both generic and diabetes-specific measures. Secondary outcome domains were controlled for multiplicity in the analyses.

RESULTS

Primary analyses showed that treatment satisfaction scores (P < 0.001) and treatment flexibility scores (P = 0.001) were higher for insulin lispro in type I diabetic patients. No other significant treatment differences were detected using the data from these 6-month crossover studies.

CONCLUSIONS

Treatment satisfaction and treatment flexibility were significantly improved in patients with type I diabetes using insulin lispro. Other HRQOL findings were comparable for insulin lispro and regular human insulin. Insulin lispro appears to have a measurable impact on lifestyle benefits in patients with type I diabetes, as demonstrated by increased treatment satisfaction and treatment flexibility.
Growth Patterns of Large-for-Gestational-Age and Appropriate-for-Gestational-Age Infants of Gestational Diabetic Mothers and Control Mothers at Age 1 Year
Authors: Vohr Betty R , McGarvey Stephen T
Published: March 2007

OBJECTIVE

The purpose of this study was to explore the development of adiposity in macrosomic and normosomic infants of mothers with gestational diabetes mellitus (GDM) and control subjects between birth and age 1 year, and assess its relation to maternal prenatal factors and neonatal factors.

RESEARCH DESIGN AND METHODS

This was a prospective observational study of 192 infants, including 47 large-for-gestational-age (LGA) infants of GDM mothers, 47 appropriate-for-gestational-age (AGA) infants of GDM mothers, 55 LGA control infants, and 44 AGA control infants who were evaluated at birth and age 1 year. Maternal prenatal and pregnancy anthropometric measurements were recorded. Multiple infant anthropometric measurements, including skinfold thicknesses, were obtained at birth and age 1 year. Regression models were run to detect the independent effects of various maternal and infant factors on 1-year child adiposity, adjusting for their effects at birth.

RESULTS

LGA infants of GDM mothers had a higher BMI, waist circumference, and abdominal skinfold at age 1 year compared with all other study groups. Among infants of GDM mothers, the mean 2-h postprandial glucose value for the second and third trimester correlated with waist circumference (r = 0.28, P < 0.04) and subscapular skinfold (r = 0.37, P < 0.007), and correlated marginally with 1-year sum of four skinfolds. Among infants of GDM mothers, a regression of 1-year sum of four skinfolds was significantly related to maternal prepregnancy weight after controlling for sum of skinfolds at birth. For control infants, the maternal glucose screen value was significantly associated with 1-year sum of skinfolds adjusted for the birth sum of skinfolds.

CONCLUSIONS

We concluded that macrosomic infants of GDM mothers have unique patterns of adiposity that are present at birth and persist at age 1 year. Further, we concluded that maternal factors, including adiposity and intrauterine fuel environment, influence the presence and distribution of adiposity for both infants of GDM mothers and control infants.