Ovarian markers and irregular menses among women with type 1 diabetes in the Epidemiology of Diabetes Interventions and Complications study.

OBJECTIVE: Women with type 1 diabetes have increased risk of infertility compared to women without diabetes even after adjustment for irregular menses, but aetiologies are incompletely understood. Our aim was to examine the prevalence of abnormalities in ovarian markers consistent with polycystic ovary syndrome in women with type 1 diabetes and associations with irregular menses and diabetes-specific variables. DESIGN, PATIENTS AND MEASUREMENTS: We conducted a secondary analysis of women in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study (DCCT/EDIC), a randomized trial and observational follow-up of intensive insulin therapy for type 1 diabetes. We included women with anti-Müllerian hormone (AMH) measurements among women not using oral contraceptives (n = 187). Initial AMH and testosterone measures were performed between EDIC years 1 and 4. History of irregular menses was assessed annually. RESULTS: The median age of women was 35 (interquartile ratio 29, 40) years; 133 (35%) had elevated AMH and 62 (17%) reported irregular menses. Twelve per cent of women had relative elevations in total testosterone. In multivariable models, lower insulin dosages were associated with higher AMH concentrations (P = .0027), but not diabetes duration, glycemic control, body mass index or irregular menses. Neither irregular menses nor diabetes-specific variables were associated with testosterone concentrations. CONCLUSIONS: Among women with type 1 diabetes in their thirties, abnormalities in ovarian markers are common and not associated with irregular menses and thus may partially account for decreased fecundity in women with type 1 diabetes.

Embryonic stem cell bank: a work proposal.

Human embryonic stem cells (hESCs) have an unlimited capacity to proliferate by a self-renewal process and can be differentiated in the three germ layers, opening doors to new clinical therapies to replace missing or damaged cells. The number of research groups and projects using human stem cells has increased largely in the last 5 yr. The creation of stem cell banks is another important step to support the advance of research in this field. Banks must be operated within the strict regulatory famework of good manufacturing practices and good laboratory practices that assure the highest quality standards and must implement a quality system that complies with international quality systems standards. It may also be appropriate to aim at an accreditation in order to assure correct laboratory practices at all times. Stem cell banks should receive the lines previously derived by other groups and hESCs should be provided for groups that justify their use in a research project previously approved by an ethical committee. The assays generally accepted as typical of hESCs together with the microbiological analysis should be performed in order to assure a consistent, reliable, and safe line for the researchers. In this article, the Andalusian Stem Cell Bank proposes a model of a stem cell banking process in order to create a flow diagram of hESC lines and, following the international initiatives in stem cells research, to achieve the full characterization of cells and a standardization of protocols that would simplify the hESCs culture.

Intensive insulin therapy with insulin lispro: a randomized trial of continuous subcutaneous insulin infusion versus multiple daily insulin injection.

OBJECTIVE: To evaluate glycemic control, hypoglycemic events, and quality of life in patients treated with continuous subcutaneous insulin infusion (CSII) and multiple daily insulin injection (MDI), with insulin lispro as the principal insulin. RESEARCH DESIGN AND METHODS: This clinical trial enrolled 27 patients with type 1 diabetes. They were randomly assigned to CSII (n = 13) or MDI (n = 14) treatment regimens. Glycemic control (HbA(1c) level) was the primary outcome and was measured monthly for 9 months. Secondary outcomes were patient reports of hypoglycemic events (recorded monthly for 9 months) and quality of life assessed at 9 months using the Diabetes Quality of Life (DQOL) questionnaire. RESULTS: A significant decrease in HbA(1c) from baseline was shown for both groups. However, the overall treatment effect (CSII - MDI) for HbA(1c) was +0.08% (95% CI -0.23 to +0.39, P > 0.10). This was significantly less than the a priori limit of +/-0.5% (P = 0.004). The relative treatment effect ([CSII - MDI]/MDI) for the overall number of hypoglycemic events was +9% (95% CI -37 to +87, P > 0.10). There were no statistically significant differences between treatment groups for any of the DQOL subscales. CONCLUSIONS: No statistically significant differences in glycemic control, reported hypoglycemic events, or quality of life were found in this study. Furthermore, a clinically significant difference of more than +/-0.5% HbA(1c) between the two regimens can be confidently ruled out. We conclude that the choice of intensive insulin therapy should be a matter of patient preference, consistent with lifestyle.

Counterregulatory hormone responses after long-term continuous subcutaneous insulin infusion with lispro insulin.

OBJECTIVE: To determine whether the long-term use of insulin lispro (LP) affects the counterregulatory hormone response to hypoglycemia. RESEARCH DESIGN AND METHODS: Ten patients (age range 26-51 years; ratio of men to women 9:1; BMI 24.9 +/- 0.48; mean HbA1c 7.84 +/- 0.25%) with IDDM, treated with continuous subcutaneous insulin infusion (CSII; Disetronic H-TRON V100) were studied using a double-blind, crossover design. Patients were randomized to LP or human regular insulin (HR) for 3 months and then crossed over to the other insulin for an additional 3 months. All meal boluses were given 0-5 min before breakfast, lunch, and dinner. Counterregulatory hormone responses to a stepped hypoglycemic clamp (consecutive glucose levels in mmol/l: 4.2; 3.5; 2.8, each for 1 h) were evaluated at the end of each treatment period. RESULTS: HbA1c was significantly lower with LP versus HR (7.47 +/- 0.28% vs. 7.9 +/- 0.26%, P = 0.04). The incidence of hypoglycemia per 30 days (capillary blood glucose < 3.0 mmol/l and/or symptoms) during the last month of the study was significantly lower with LP versus HR (8.7 +/- 2.9 vs. 11.8 +/- 2.9, P = 0.03). The total daily insulin dosage was not different in the two treatment periods. There was no episode of severe hypoglycemia or diabetic ketoacidosis. The peak growth hormone, cortisol, glucagon, and epinephrine responses during the same period of hypoglycemia were not different for each treatment period. CONCLUSIONS: The use of LP in CSII results in improved glycemic control and a decrease in the frequency of hypoglycemia without adversely affecting counterregulatory hormone response to hypoglycemia.

The prevalence of NIDDM and associated risk factors in native Canadians.

OBJECTIVE: To determine the true prevalence of impaired glucose tolerance (IGT), NIDDM, and associated risk factors by age and sex in an isolated native community. RESEARCH DESIGN AND METHODS: A community-wide prevalence survey using a 75-g oral glucose tolerance test (OGTT) was undertaken in the remote native reserve of Sandy Lake, Ontario, Canada. Measurements for obesity included waist-to-hip circumference, BMI, and percentage body fat. RESULTS: A total of 728 individuals were enrolled, representing a community participation rate of 72%. The overall crude prevalence of NIDDM was 17.2% (18.1% females and 16.0% males) and increased to 26.1% overall (28.0% females and 24.2% males) when age-standardized. The prevalence of IGT was higher in females compared with males (age-standardized prevalence of 19.8 vs. 7.1%, respectively). Females had a higher prevalence of obesity, IGT, and NIDDM occurring at younger ages. Measures of obesity and fasting insulin levels were significantly associated with NIDDM in the 18-49 age-group. CONCLUSIONS: The prevalence rates of NIDDM in this study population are the highest reported to date in a Canadian native population and among the highest reported in the world. Females appear to be at much higher risk of developing obesity, IGT, and NIDDM and at a younger age. Due to the high prevalence rates of IGT and NIDDM in this young population, there is urgent need to develop culturally appropriate community-based public health intervention programs before the long-term complications of diabetes have a devastating effect on the residents.

The relationship of cardiac diastolic dysfunction to concurrent hormonal and metabolic status in type I diabetes mellitus.

The presence of diabetic cardiomyopathy and its relationship to concurrent hormonal and metabolic status have not been defined in patients with uncomplicated type I diabetes mellitus. Accordingly, radionuclide left ventricular angiograms and simultaneous metabolic profiles were obtained in 8 type I diabetic patients who had no major diabetic complications and in 11 normal subjects. Occult coronary artery disease was excluded by electrocardiogram exercise testing. Hemodynamics and systolic function did not differ between the groups. However, the peak filling rate (PFR; end-diastolic volumes per s) was less in the diabetic patients at rest [mean, 4.1 +/- 0.2 (+/- SE) vs. 4.8 +/- 0.2; P less than 0.05] and during aerobic (6.8 +/- 0.2 vs. 8.30 +/- 0.3; P less than 0.01) and anaerobic exercise (8.8 +/- 0.3 vs. 9.8 +/- 0.4; P less than 0.05). The time to PFR was prolonged in the diabetic patients at rest (174 +/- 10 vs. 133 +/- 7 ms; P less than 0.01) and during anaerobic exercise (126 +/- 5 vs. 103 +/- 6 ms; P less than 0.01). Plasma glucose and insulin levels were elevated in the diabetic patients at rest and during exercise. Otherwise, the metabolic and hormonal levels did not differ between the groups. In the diabetic patients, no single metabolic or hormonal parameter correlated with PFR or time to PFR. Impairment of diastolic filling also did not correlate with level of glycosylated hemoglobin or duration of diabetes. The alteration in diastolic filling present in type I diabetic patients who have no other diabetic complications may represent the earliest functional effect of diabetic cardiomyopathy.

Effect of mitomycin-C on human foreskin fibroblasts used as feeders in human embryonic stem cells: immunocytochemistry MIB1 score and DNA ploidy and apoptosis evaluated by flow cytometry.

Mitomycin C (MMC) treatment has been used to arrest cell proliferation but not much is known about the effect of MMC on human foreskin fibroblasts (HFF) used as feeders for human embryonic stem cells (hESC). We tested the ability of MMC to stop the proliferation of HFF and to induce apoptosis. MMC inhibited the proliferation of HFF at 10 microg/ml over 2.5h of MMC treatment showing a decrease in the proliferation index measured by Ki-67 and S and G2/M phases related to active HFF. A low percentage of cells showed necrotic or apoptotic features using different lengths of incubation. Over time, the majority of cells remained in a mitotically inactive state. The percentage of apoptotic cells increased from day 2 to day 10, at the same time as the necrotic ones increased. The HS181 hESC line grew in an undifferentiated state on inactive HFF throughout the study.

Body image concepts differ by age and sex in an Ojibway-Cree community in Canada.

Community-based studies of body image concepts can be useful for developing health interventions to prevent obesity-related diseases such as diabetes and cardiovascular disease in specific populations. First Nations peoples, in particular, face increased obesity-related health problems as a result of acculturative changes in diet and activity. This study examined body shape perception in an Ojibway-Cree community in Northern Ontario, Canada. A set of figure outline drawings ranging from very thin to very obese were used to examine perceived body shape, body shape satisfaction and ideals of healthiness across sex and age groups. Overall, only 16% of the population were satisfied with their current body shape. People with a higher body mass index (BMI) were less satisfied with their bodies and thought they were less healthy than people with a lower BMI. While females had a significantly greater BMI than males, males and females did not differ significantly in perception of current body shape. On the other hand, females desired relatively smaller body shapes than males (P < 0.05). Older people chose significantly larger healthy body shapes than did younger people (P < 0.05). Differences between our results and those reported for Anglo populations indicate that while both groups prefer body shapes smaller than those they have currently, the Ojibway-Cree tend to prefer relatively larger body shapes. Knowledge of age and sex-related patterns of body image concepts in communities can assist in the design of obesity-reducing interventions targeting specific groups.

Use of ethnographic methods for applied research on diabetes among the Ojibway-Cree in northern Ontario.

This article presents the results of applied ethnographic research aimed at developing a community-based diabetes prevention program in an isolated Ojibway-Cree community in northern Ontario. Using qualitative techniques, the authors describe diabetes in its sociocultural context and underlying belief systems that affect related activity and dietary behaviors. Local concepts of food and illness are dichotomized into "Indian" and "white man's" groupings, with Indian foods perceived as healthy and white man's foods felt to be unhealthy. Diabetes is believed to result from consumption of white man's "junk foods" (sugar, soda); some believe the disease can be avoided by eating traditional Indian foods such as game animals (moose, beaver, duck). While dietary linkages to diabetes are recognized, physical activity as a means of controlling obesity and decreasing the risk for diabetes is not part of the local ethnomedical model. This information is being used to develop culturally appropriate health education interventions.

The use of bioelectrical impedance analysis (BIA) to estimate body composition in the Diabetes Control and Complications Trial (DCCT).

Although weight gain often accompanies intensive treatment regimens designed to achieve near-normal glycemia in insulin-dependent diabetes mellitus (IDDM), body composition (BC) has not been well studied. Bioelectrical impedance analysis (BIA) is a safe, rapid, and non-invasive method of assessing BC but has not been utilized widely in IDDM. Data from 46 adults with IDDM were used to develop a regression model estimating fat-free body mass (FFM) from bioimpedance measurements obtained using a proximal electrode placement. Reference values of FFM were determined by dual x-ray absorptiometry (DXA). A model using the ratio of height squared to the minimum resistance of 4 limb-lead combinations (H2/R), total body weight, and a weight-gender interaction achieved a high level of accuracy (R2 = 0.982, residual standard deviation = 1.43 kg), while studies of 10 subjects before and after a light meal found no short-term effect of glycemia on measured BIA variables. BIA will therefore be used in combination with waist-to-hip ratios to study the composition and distribution of the increased weight associated with intensive therapy in the DCCT.