OBJECTIVE -Phytoestrogen consumption has been shown to reduce risk factors for cardiovascular disease. Type 2 diabetes confers an adverse cardiovascular risk profile particularly in women after menopause. The aim of this study was to determine whether a dietary supplement with soy protein and isoflavones affected insulin resistance, glycemic control, and cardiovascular risk markers in postmenopausal women with type 2 diabetes. RESEARCH DESIGN AND METHODS-A total of 32 postmenopausal women with diet-controlled type 2 diabetes completed a randomized, double blind, cross-over trial of dietary supplementation with phytoestrogens (soy protein 30 g/day, isoflavones 132 mg/day) versus placebo (cellulose 30 g/day) for 12 weeks, separated by a 2-week washout period.RESULTS -Compliance with the dietary supplementation was Ͼ90% for both treatment phases. When compared with the mean percentage change from baseline seen after 12 weeks of placebo, phytoestrogen supplementation demonstrated significantly lower mean values for fasting insulin (mean Ϯ SD 8.09 Ϯ 21.9%, P ϭ 0.006), insulin resistance (6.47 Ϯ 27.7%, P ϭ 0.003), HbA 1c (0.64 Ϯ 3.19%, P ϭ 0.048), total cholesterol (4.07 Ϯ 8.13%, P ϭ 0.004), LDL cholesterol (7.09 Ϯ 12.7%, P ϭ 0.001), cholesterol/HDL cholesterol ratio (3.89 Ϯ 11.7%, P ϭ 0.015), and free thyroxine (2.50 Ϯ 8.47%, P ϭ 0.004). No significant change occurred in HDL cholesterol, triglycerides, weight, blood pressure, creatinine, dehydroepiandrosterone sulfate, androstenedione, and the hypothalamic-pituitary-ovarian axis hormones.CONCLUSIONS -These results show that dietary supplementation with soy phytoestrogens favorably alters insulin resistance, glycemic control, and serum lipoproteins in postmenopausal women with type 2 diabetes, thereby improving their cardiovascular risk profile. Diabetes Care 25:1709 -1714, 2002C ardiovascular diseases (CVDs), especially coronary heart disease and cerebrovascular disease, are the leading causes of death in women (1). Type 2 diabetes increases the risk of death from CVD by two-to fourfold (2), and women with diabetes are four times more likely to die from CVD than men (3). Postmenopausal estrogen depletion (4) and increased insulin resistance (5) may contribute to the high risk of accelerated CVD in women with type 2 diabetes.Epidemiological data suggest that in Japanese-Americans in Seattle, WA, the prevalence of type 2 diabetes is four times that in Japanese in Tokyo (6,7). Despite very similar degrees of hyperglycemia, the Japanese-Americans with type 2 diabetes showed significantly higher levels of plasma insulin after a 75-g oral glucose tolerance test (OGTT) than Japanese with diabetes (6,8), and BMI correlated with insulin levels only for the JapaneseAmerican men (8). This observation suggested a greater degree of insulin resistance among the Japanese-Americans and that factors other than BMI were responsible for the difference in plasma insulin levels between the two groups (9). Soy is a staple in the diet of the Japanese population, and consumption of soy has ...

The allocation of hypoglycaemic symptoms to autonomic or neuroglycopenic groups tends to occur on an a priori basis. In view of the practical need for clear symptom markers of hypoglycaemia more scientific approaches must be pursued. Substantial evidence is presented from two large scale studies we performed which support a three factor model of hypoglycaemic symptomatology, based on the statistical associations discovered among symptoms reported by diabetic patients. Study 1 involved 295 insulin-treated out-patients and found that 11 key hypoglycaemic symptoms segregated into three clear factors: autonomic (sweating, palpitation, shaking and hunger) neuroglycopenic (confusion, drowsiness, odd behaviour, speech difficulty and incoordination), and malaise (nausea and headache). The three factors were validated on a separate group of 303 insulin-treated diabetic out-patients. Confirmatory factor analyses showed that the three factor model was the optimal model for explaining symptom covariance in each group. A multi-sample confirmatory factor analysis tested the rigorous assumptions that the relative loadings of symptoms on factors across groups were equal, and that the residual variance for each symptom was identical across groups. These assumptions were successful, indicating that the three factor model was replicated in detail across these two large samples. It is suggested that the results indicate valid groupings of symptoms that may be used in future research and in clinical practice.

National Institute for Health Research and University of Hull.

To estimate the frequency and morbidity of insulin-induced hypoglycaemia, a retrospective survey was undertaken of the frequency of severe hypoglycaemia in 600 randomly selected patients with insulin-treated diabetes who were attending a large diabetic outpatient clinic in a teaching hospital. The resulting morbidity (hypoglycaemia-related injuries, convulsions, and road traffic accidents) was ascertained in 302 patients. One hundred and seventy-five (29.2%) of the 600 patients reported a total of 964 episodes of severe hypoglycaemia in the preceding year, giving an overall frequency for the group of 1.60 episodes patient-1year-1. The frequency of severe hypoglycaemia which was documented in 544 Type 1 (ketosis prone) diabetic patients was double that observed in a subgroup of 56 Type 2 diabetic patients who were being treated with insulin (1.70 vs 0.73 episodes patient-1year-1). In the subset of 302 patients, those who had experienced severe hypoglycaemia had greater morbidity associated with an estimated rate of injury of 0.04 injuries person-1year-1. Twenty (6.6%) patients reported a total of 37 convulsions associated with hypoglycaemia, 5 of which had occurred in the preceding year (0.02 convulsions person-1year-1). Five patients reported road traffic accidents in the preceding year which had been caused by hypoglycaemia. The only reliable predictors of severe hypoglycaemia were a history of previous severe hypoglycaemia (p < 0.001), a history of hypoglycaemia-related injury (p < 0.001) or convulsion (p < 0.001), and the duration of insulin therapy (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

To examine the hypothesis that episodes of severe hypoglycaemia may cause cumulative cognitive impairment. 100 Type 1 (insulin-dependent) diabetic patients were examined. Their age range was 25-52 years, and the onset of diabetes had occurred after the age of 19 years. Patients with evidence of organic brain disease, including cerebrovascular disease, were excluded. A questionnaire was used to assess the number, frequency and severity of hypoglycaemic episodes experienced during treatment with insulin and the accuracy of this retrospective information was verified from general practice and hospital case-notes. A detailed neuropsychological assessment was undertaken, including tests of pre-morbid and present IQ (Wechsler-Revised), memory and information-processing speed. Significant correlations were observed between the frequency of severe hypoglycaemia and the magnitude of intellectual decline, Performance IQ, inspection time and reaction time (patients with the more frequent hypoglycaemia had poorer performance). Two sub-groups of patients were identified on the basis of their experience of severe hypoglycaemia, and were balanced for pre-morbid IQ, age and duration of diabetes. One sub-group (n = 23) had never experienced severe hypoglycaemia (Group A), whilst the other sub-group (n = 24) had suffered at least five episodes of severe hypoglycaemia (Group B). Group B had greater intellectual impairment than Group A, and Group B also had a significantly slower mean reaction time and higher reaction time variance when compared with Group A.

Three-hundred and two insulin-treated diabetic patients were questioned about hypoglycaemia using a structured questionnaire interview. Two-hundred and twenty-six patients (75%) had normal symptomatic awareness, 48 (16%) had partial awareness, 21 (7%) had absent awareness of hypoglycaemia, and 7 (2%) denied ever experiencing hypoglycaemia. Patients with complete loss of awareness of hypoglycaemia had diabetes of longer duration; none had a HbA1 concentration within the non-diabetic range. Loss of awareness of hypoglycaemia was associated with an increased incidence of severe hypoglycaemia, 19 (91%) of the patients with absent awareness, and 33 (69%) with partial awareness of hypoglycaemia experiencing severe hypoglycaemia over 1 year compared with only 41 (18%) of patients with normal awareness of hypoglycaemia (p less than 0.001). Cardiovascular autonomic function tests were performed in 226 (75% of the whole group). Of the patients who had diabetes for more than 15 years, 54% (n = 39) with normal awareness of hypoglycaemia, compared with 59% (n = 10) with absent awareness of hypoglycaemia, had evidence of cardiovascular autonomic impairment (NS). Seven (41%) of the 17 patients with absent awareness of hypoglycaemia and diabetes of greater than 15 years duration had no evidence of autonomic dysfunction. Loss of hypoglycaemia awareness is a common problem in patients with insulin-treated diabetes of long duration, is associated with an increased incidence of severe hypoglycaemia, but is not invariably associated with abnormal cardiovascular autonomic function tests.

This study demonstrated the high frequency with which neuroglycopenic symptoms occur at the onset of hypoglycemia and the symptoms that could be used by an individual patient as a warning of the development of acute hypoglycemia, although the rapid reduction of plasma glucose is faster than experienced by the ambulant diabetic patient. Factor analysis assisted with the allocation of symptoms to either the autonomic or neuroglycopenic groupings, but the allocation of some symptoms remained undefined, and care must be taken when assessing symptoms such as hunger, weakness, blurred vision, and drowsiness when comparing the frequency of autonomic versus neuroglycopenic symptoms. To reduce the confusion resulting from the use of different symptom questionnaires in studies of hypoglycemia, a sample questionnaire is presented, the development of which was assisted by our analysis.

controlled for in the multivariate analvsis. Furthermore, the suggested risk factors occurring later in life, such as psychological mechanisms and drug availability and exposition, cannot explain the demonstrated associations between administration of drugs during the perinatal period and subsequent addiction in offspring. Also, genetic and socioeconomic factors were largely controlled for by matching addicts with their own siblings.In conclusion, effective pain relief is sometimes an important factor for a successful outcome of delivery, as well as for the ability of the mother to accept and care for the child in the future. At present, when considering the choice of analgesic method immediate risks and benefits are mainly taken into account. When depressant or sedative drugs are used their possible long term effects due to imprinting also seem to be important. From this point of view, analgesic methods not associated with passage of substantial amounts of drugs across the placenta are preferable. Our Abstract Objective-To see whether a prepregnancy clinic for diabetic women can achieve tight glycaemic control in early pregnancy and so reduce the high incidence of major congenital malformation that occurs in the infants of these women. Design-An analysis of diabetic control in early pregnancy including a record of severe hypoglycaemic episodes in relation to the occurrence of major congenital malformation among the infants.Setting-A diabetic clinic and a combined diabetic and antenatal clinic of a teaching hospital.Patients -143 Insulin dependent women attending a prepregnancy clinic and 96 insulin dependent women managed over the same period who had not received specific prepregnancy care.Main outcome measure-The incidence of major congenital malformation.Results-Compared with the women who were not given specific prepregnancy care the group who attended the prepregnancy clinic had a lower haemoglobin Al concentration in the first trimester (8.4% v 10-5%), a higher incidence of hypoglycaemia in early pregnancy (38/143 women v 8/96), and fewer infants with congenital abnormalities (2/143 v 10/96; relative risk among women not given specific prepregnancy care 7-4 (95% confidence interval 1-7 to 33.2)).Conclusion-Tight control of the maternal blood glucose concentration in the early weeks of pregnancy can be achieved by the prepregnancy clinic approach and is associated with a highly significant reduction in the risk of serious congenital abnormalities in the offspring. Hypoglycaemic episodes do not seem to lead to fetal malformation even when they occur during the period of organogenesis.