Low birth weight (LBW) is an important risk factor for type 2 diabetes. We have developed a mouse model of LBW resulting from undernutrition during pregnancy. Restriction of maternal food intake from day 12.5 to 18.5 of pregnancy results in a 23% decrease in birth weight (P < 0.001), with normalization after birth. However, offspring of undernutrition pregnancies develop progressive, severe glucose intolerance by 6 months. To identify early defects that are responsible for this phenotype, we analyzed mice of undernutrition pregnancies at age 2 months, before the onset of glucose intolerance. Fed insulin levels were 1.7-fold higher in mice of undernutrition pregnancies (P ‫؍‬ 0.01 vs. controls). However, insulin sensitivity was normal in mice of undernutrition pregnancies, with normal insulin tolerance, insulin-stimulated glucose disposal, and isolated muscle and adipose glucose uptake. Although insulin clearance was mildly impaired in mice of undernutrition pregnancies, the major metabolic phenotype in young mice of undernutrition pregnancies was dysregulation of insulin secretion. Despite normal ␤-cell mass, islets from normoglycemic mice of undernutrition pregnancies showed basal hypersecretion of insulin, complete lack of responsiveness to glucose, and a 2.5-fold increase in hexokinase activity. Taken together, these data suggest that, at least in mice, primary ␤-cell dysfunction may play a significant role in the pathogenesis of LBW-associated type 2 diabetes. Diabetes 54: 702-711, 2005

Background/Aim: Nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency (NC-CAH) is associated with hyperandrogenemia, chronic anovulation, hirsutism, acne and adrenal hyperplasia. A few studies have shown hyperinsulinemia and insulin insensitivity in NC-CAH. Hyperinsulinemia can stimulate leptin secretion, and androgens can inhibit leptin secretion. Thus, we designed a study to investigate the insulin levels and insulin sensitivity and the effect of chronic endogenous hyperinsulinemia and androgens on leptin in patients with NC-CAH. Methods: Eighteen women with untreated NC-CAH and 26 normally cycling control women with a similar body mass index (BMI) were studied. Basal hormones, fasted and fed insulin levels, leptin and stimulated 17-hydroxyprogesterone (17-OHP) concentrations were studied. Homeostasis model assessment was used to assess insulin sensitivity. Results: The basal 17-OHP, the free testosterone (fT) and dehydroepiandrosterone sulfate (DHEA-S) were significantly different in the 2 groups (p < 0.05). Fasting and fed insulin levels of the NC-CAH group were higher than those of the control group (p < 0.05) and insulin sensitivity was lower in NC-CAH than in controls (p < 0.05). Insulin levels were correlated with fT and 17-OHP (p < 0.05). Serum leptin levels for NC-CAH (25.9 ± 12.5 µg/l) did not differ from the controls (25.4 ± 12.06 µg/l) and were positively correlated with BMI (r = 0.725) and percent body fat (r = 0.710) for both groups (both p < 0.001). Leptin levels were not correlated with estrogen or androgens, gonadotropins or insulin levels. Conclusion: Hyperinsulinemia and insulin insensitivity associated with hyperandrogenism were detected in untreated NC-CAH patients as in previous reports, whereas serum leptin levels did not differ from those of controls.

The aim of this study is to evaluate the awareness, perception, sources of information, and knowledge of osteoporosis in a sample of rural Turkish women, to examine the factors related to their knowledge, and organize effective education programs. A total of 768 women mean age 53.6 +/- 8.2 (40-70) were randomly selected and interviewed during their visits to primary care centers in three rural towns in West Anatolia. A structured questionnaire was administered by trained nurses. Chi-squared test was performed in age and educational level groups for revealing factors influencing the awareness, perception, and knowledge sources of osteoporosis. One-way analysis of variance (ANOVA) analysis was carried out in calculating the difference of knowledge scores among groups. Of the women, 60.8% had heard of and 44.9% had the correct definition for osteoporosis. Awareness and accurate definition of osteoporosis was high in younger and high educated women (p < 0.001). Television was the main source of knowledge with the rate of 55%, doctors and nurses/midwives were the second and third sources, respectively. Osteoporosis knowledge was low with a mean score of 5.52 out of 20. Younger and more educated women had higher knowledge scores. Low calcium in diet and menopause were the first two risk factors chosen for osteoporosis. Knowledge about osteoporosis among rural Turkish women is low, and majority of women are unaware of the risk factors and consequences of osteoporosis. Therefore, appropriate educational programs should be planned according to community needs, and the target of these programs should be less educated and older women.

Abstract. Leptin is considered to play a role in maintenance of energy balance and body weight by neuroendocrine mechanisms. The physiological mechanisms for thyroid hormone-induced alteration in serum leptin are not well known. In the present study, the relationship between thyroid hormones and leptin levels was investigated in patients with overt hypothyroidism and hyperthyroidism before and after successful treatment. Leptin levels were determined by radioimmunoassay and body mass index (BMI) was calculated for each subject. Serum leptin levels of 26 hypothyroid and 22 hyperthyroid patients were compared with those of 20 healthy volunteers who comprised the controls. Serum leptin levels of hypothyroid patients (28.4 ± 4.1 ng/ml) were found to be significantly higher than the controls (19.1 ± 3.2 ng/ml) (p<0.01), whereas hyperthyroid patients had lower levels (10.7 ± 1.2 ng/ml) (p<0.01). In hypothyroid patients, serum leptin levels were decreased significantly to 20.6 ± 2.1 ng/ml with thyroxin treatment (p<0.05). However, in hyperthyroid group, serum leptin levels were increased to 12.4 ± 2.2 ng/ml by treatment (p>0.05). BMI was not changed with the treatment in either group. The serum leptin levels were correlated with BMI and thyrotropin (TSH) in both hypothyroid and hyperthyroid patients. Serum leptin levels are affected in thyroid disorders and the correlation of leptin with TSH is independent of thyroid hormones.

Aims/hypothesis Observational studies in humans suggest that low birthweight may decrease the risk of type 1 diabetes, but the mechanism is unknown. We hypothesised that antenatal undernutrition would decrease the incidence of type 1 diabetes in non-obese diabetic (NOD) mice. Materials and methods A 40% restriction of energy intake was applied to pregnant NOD dams from day 12.5 to day 18.5 of gestation, resulting in intrauterine growth retardation of offspring. All mice were fed a standard diet after weaning. Control and undernourished female offspring were followed to assess diabetes incidence. Male NOD mice were treated with cyclophosphamide to accelerate development of diabetes. Glucose homeostasis, body composition and pancreatic histology were compared in control and undernourished offspring. Results Mean birthweight was lower in undernourished than in control mice (p=0.00003). At 24 weeks of age, the cumulative incidence of spontaneous diabetes in female mice was 73% in control and 48% in undernourished mice (p=0.003). In cyclophosphamide-treated male mice, antenatal undernutrition also tended to reduce the development of diabetes (p=0.058). Maternal leptin levels were lower in undernourished dams on day 18.5 of pregnancy (p=0.039), while postnatal leptin levels were significantly higher in undernourished offspring at 4, 20 and 27 weeks of life (p<0.05). Beta cell mass was similar in both groups (control = 0.4 mg; undernourished = 0.54 mg; p=0.24). Histological evidence of apoptosis at 20 weeks was greater in control than in undernourished mice (control = 6.3± 1.4%; undernourished = 4.2±0.3%, p=0.05). Conclusions/interpretation Antenatal undernutrition reduces the incidence of diabetes in NOD mice, perhaps via alterations in apoptosis.