Ethnic variation in the activity of lipid desaturases and their relationships with cardiovascular risk factors in control women and an at-risk group with previous gestational diabetes mellitus: a cross-sectional study.

BACKGROUND: Lipid desaturase enzymes mediate the metabolism of fatty acids to long chain polyunsaturated fatty acids and their activities are related to metabolic risk factors for Type 2 diabetes (T2DM) and coronary heart disease (CHD). There are marked ethnic differences in risks of CHD and T2DM but little is known about ethnic differences in desaturase activities. METHODS: Samples from a study of CVD risk in women with previous gestational diabetes were analysed for percentage fatty acids in plasma free fatty acid, triglyceride, cholesterol ester and phospholipid pools for 89 white European, 53 African Caribbean and 56 Asian Indian women. The fatty acid desaturase activities, stearoyl-CoA desaturase (SCD, calculated separately for C16 and C18 fatty acids), delta 6 desaturase (D6D) and delta 5 desaturase (D5D) were estimated from precursor-to-product ratios and their relationships with adiposity, blood pressure, cholesterol, triglycerides, HDL cholesterol and insulin sensitivity explored. Ethnic differences in desaturase activities independent of ethnic variation in risk factor correlates of desaturase activities were then identified. RESULTS: There was significant ethnic variation in age, BMI, waist circumference, blood pressure, serum triglycerides and HDL cholesterol concentrations and insulin resistance. Desaturase activities showed significant correlations, independent of ethnicity, with BMI, waist circumference, triglycerides and HDL cholesterol. Independent of ethnic variation in BMI, waist circumference, triglycerides and HDL cholesterol, SCD-16 activity, calculated from each of the four lipid pools measured, was 18-35 percent higher in white Europeans than in African Caribbeans or Asian Indians (all p < 0.001). Similar, though less consistent differences were apparent for SCD-18 activity. Also independently of risk factor variation, but specifically when calculated from the cholesterol ester and phospholipid, pools, D6D activity was significantly lower in Asian Indians, and D5D activity higher in African Caribbeans. CONCLUSIONS: Significant ethnic differences exist in desaturase activities, independently of ethnic variation in other risk factors. These characteristics did not accord with higher risk of T2DM among African Caribbeans and Asian Indians nor with lower risk of CHD among African Caribbeans but did accord with the higher risk of CHD in Asian Indians.

Bisphenol A correlates with fewer retrieved oocytes in women with tubal factor infertility.

PURPOSE: Serum and urinary bisphenol A (BPA) concentrations have been associated negatively with the number of retrieved oocytes after in vitro fertilization (IVF). The impact of BPA upon women with polycystic ovary syndrome (PCOS) and women with tubal factor infertility (TFI), following IVF, was investigated. To this purpose, associations among serum and urinary and follicular fluid (FF) BPA concentrations and the number of retrieved and fertilized oocytes and comparisons between pregnancy rates were evaluated. METHODS: This was a cross-sectional study conducted at a university-affiliated assisted conception unit between January and November 2019, including 93 women of reproductive age (PCOS: 45; TFI: 48) following IVF. Unconjugated FF and serum BPA concentrations and total urinary BPA concentration were measured using a novel gas chromatography-mass spectrometry method. The number of retrieved and fertilized oocytes and pregnancy rate were documented and evaluated. RESULTS: The number of oocytes retrieved from PCOS women was greater than that of 21 TFI women, independently of BMI. Lower FF BPA concentrations were found in all PCOS women and in overweight/obese PCOS compared to TFI women (0.50, 0.38, and 1.13 ng/mL, respectively). In TFI women, FF BPA concentrations correlated negatively with the number of retrieved oocytes. Serum and FF and urinary BPA concentrations did not significantly affect the number of fertilized oocytes and pregnancy rate in both groups. CONCLUSION: FF BPA concentrations were lower in all PCOS women and in overweight/obese PCOS than in TFI women. In TFI women, FF BPA concentrations correlated negatively with retrieved oocytes. Confirmation of these findings might lead to moderation of use of BPA-containing products by women undergoing IVF.

Primary pigmented nodular adrenocortical disease: a case report in a 7-year-old girl.

Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of Cushing syndrome in children, often occurring in association with Carney complex. We report a case of Cushing syndrome due to isolated non-familial PPNAD. The child presented with typical clinical characteristics, growth retardation and obesity. Liddle's test was positive but micronodular appearance was not evident on CT scan and MRI; selective venous sampling revealed higher cortisol concentrations in the right adrenal vein. The patient underwent a laparoscopic right adrenalectomy. Postoperatively, hypercortisolism signs disappeared but after the second year a slight increase in urinary cortisol was noted and the patient developed osteopenia. Although significant catch-up growth occurred postoperatively, height did not normalize over the next 2 years. When she entered puberty, treatment with a luteinizing-hormone-releasing hormone agonist was initiated and growth hormone was added. Almost 5 years later a left adrenalectomy was also performed. Thereafter, complete disease remission was observed, the patient's growth accelerated and her osteopenia reversed.

Sex determination and disorders of sex development according to the revised nomenclature and classification in 46,XX individuals.

There have been considerable advances concerning understanding of the early and later stages of ovarian development; a number of genes have been implicated and their mutations have been associated with developmental abnormalities. The most important genes controlling the initial phase of gonadal development, identical in females and males, are Wilms' tumor suppressor 1 (WT1) and steroidogenic factor 1 (SF1). Four genes are likely to be involved in the subsequent stages of ovarian development (WNT4, DAX1, FOXL2 and RSPO1), but none is yet proven to be the ovarian determining factor. Changes in nomenclature and classification were recently proposed in order to incorporate genetic advances and substitute gender-based diagnostic labels in terminology. The term "disorders of sex development" (DSD) is proposed to substitute the previous term "intersex disorders". Three main categories have been used to describe DSD in the 46,XX individual: 1) disorders of gonadal (ovarian) development: ovotesticular DSD, previously named true hermaphroditism, testicular DSD, previously named XX males, and gonadal dysgenesis; 2) disorders related to androgen excess (congenital adrenal hyperplasia, aromatase deficiency and P450 oxidoreductase deficiency); and 3) other rare disorders. In this mini-review, recent advances concerning development of the genital system in 46,XX individuals and related abnormalities are discussed. Basic embryology of the ovary and molecular pathways determining ovarian development are reviewed, focusing on mutations disrupting normal ovarian development. Disorders of sex development according to the revised nomenclature and classification in 46,XX individuals are summarized, including genetic progress in the field.

Long-Term Metabolic Consequences in Patients with a History of Gestational Diabetes.

Gestational diabetes mellitus is a common metabolic complication of pregnancy. Universal guidelines on gestational diabetes have been impeded by the long-term controversies on its definition and screening strategies. The prevalence of gestational diabetes is rising all over the world, is significantly influenced by ethnicity and its rise is mainly attributed to increasing maternal obesity and age. Gestational diabetes mellitus has important long-term implications, including gestational diabetes recurrence, increased risk for developing type 2 diabetes, metabolic syndrome and cardiovascular disease for the mother. Gestational diabetes mellitus may be viewed as a chronic metabolic disorder that is identified in women during gestation and may provide a unique opportunity for the early identification and primary prevention of type 2 diabetes mellitus and cardiovascular disease in these women. In this mini-review, the evolution of screening tests for gestational diabetes and guidelines are briefly described and metabolic and cardiovascular long-term consequences of women with a history of gestational diabetes are summarized. A summary of our own St. Mary's Hospital-UK Research series on long-term metabolic consequences of 368 women with a history of gestational diabetes of 3 different ethnic groups and 482 control women is also included. We found that approximately 2 years following delivery, 37% of women with a history of gestational diabetes had abnormal glucose concentrations, but, most importantly, even those who were normoglycaemic, postpartum displayed metabolic abnormalities on detailed testing. Future research needs to focus on the prevention of gestational diabetes long-term complications, but also in identification of pre-pregnancy predictors and risk reduction before conception.

Pleiotropic genetic syndromes with developmental abnormalities associated with obesity.

Childhood obesity is a common and complex problem that may persist in adulthood. It may present as a component of genetic syndromes associated with dysmorphic features, developmental abnormalities, mental retardation and/or learning disabilities and often neuroendocrine dysfunction. Although the chromosomal abnormalities of these rare syndromes are already known, the specific genetic and pathophysiological mechanisms leading to the distinct phenotypes and obesity still remain unclarified. New exciting genetic pathways contributing to syndrome phenotype and leading to obesity have recently been identified. Prader-Willi syndrome is caused by loss of expression of the C/D box HBII-84 cluster of snoRNAs. Dysfunction of the primary cilium, thought to have important signalling functions, may contribute to disease phenotype and obesity in Bardet-Biedl, Alstrom and Carpenter syndromes. In this mini-review current knowledge of clinical and genetic characteristics is summarized as well as the pathogenesis of these syndromes with special emphasis on the pathogenesis of obesity.

Serum Bisphenol A concentrations in men with idiopathic infertility.

BACKGROUND: Bisphenol A (BPA) has been associated with male reproductive dysfunction. However, few studies have assessed BPA according to the cause of male infertility. AIM: To investigate serum BPA concentrations in infertile men according to infertility cause. PATIENTS AND METHODS: Men with infertility (n = 55) [non-obstructive azoospermia (n = 23), cryptorchidism (n = 12), varicocele (n = 20)] compared with fertile men (n = 25). Serum BPA concentrations were measured along with clinical and hormonal assessment. RESULTS: BPA was detected in all men, with no difference between infertile and control groups [median (IQR) 0.19 (0.45) vs. 0.18 (0.28) ng/ml, p = 0.689] or among the infertility cause [azoospermia 0.30 (0.69), cryptorchidism 0.12 (0.39), varicocele 0.17 (0.23) ng/ml, p = 0.316]. High concentrations of BPA (>3 ng/ml) were observed only in infertile men. Α negative correlation was observed between ΒΡΑ concentrations and AMH (r = -0.320, p < 0.01). CONCLUSIONS: Although male infertility cannot be attributed to exposure to BPA, high concentrations of BPA could contribute to infertility.

Growth hormone deficiency in a patient with autoimmune polyendocrinopathy type 2.

Autoimmune polyglandular syndrome (APs) type 2 is characterized by the presence of Addison's disease, in association with autoimmune thyroid disease and/or type 1 diabetes mellitus and is rare in children. A 12.5 yr old prepubertal boy presented with symptoms related to Addison's disease and a large goiter. He was euthyroid with positive thyroid antibodies, low cortisol, aldosterone and very high adrenocorticotropin (ActH) and renin levels. Growth hormone (GH) secretion and an MrI scan of the pituitary were normal. He was started on hydrocortisone, fludrocortisone and subsequently on L thyroxine. Eighteen months later, decreased growth rate was noted and GH deficiency was detected, apparently secondary to autoimmune hypophysitis. Interestingly, he did not develop any other pituitary hormone deficiencies. He was started on GH therapy and had a good treatment response in the next 3 years. the combination of adrenal and thyroid insufficiencies with autoimmune hypophysitis is a very rare manifestation of APs-type 2. GH deficiency as the only symptom of lymphocytic hypophysitis is extremely rare. In children with autoimmune polyendocrine disorders, careful monitoring of growth is needed. In the case of low growth rate, GH should be evaluated by dynamic tests and, if GH deficiency is detected, treatment with hGH must be initiated.

Early metabolic defects following gestational diabetes in three ethnic groups of anti-GAD antibodies negative women with normal fasting glucose.

OBJECTIVE: To characterise early metabolic abnormalities and the impact of ethnicity following gestational diabetes mellitus (GDM). DESIGN: Women with a history of GDM belonging to three different ethnic groups were evaluated. Using the insulin-modified, frequently-sampled intravenous glucose tolerance test (FSIVGTT) and HOMA we studied 34 European, 16 South Asian and 10 Afro-Caribbean women with normal fasting glucose following GDM and 44 European, 16 South Asian and 19 Afro-Caribbean controls to assess insulin action and secretion. RESULTS: European post-GDM women had lower insulin sensitivity by FSIVGTT [0.6 (0.1-5.1) vs 1.5 (0.8-2.8) x10(-4).min(-1).pmol(-1).l(-1), p=0.010, adjusted for BMI p=0.054] and by HOMA [72(22-235) vs 153(55-421)%, p=0.004, adjusted for BMI p=0.006], and reduced -cell function [lower disposition index 0.05(0.01-0.40) vs 0.11(0.05-0.25)min(-1), p=0.017] compared with controls. South Asian post-GDM women had decreased -cell function [lower HOMA (%B) (73 (37-147) vs 124 (59-262) %, p=0.048 and acute insulin response to glucose (463 (131-1639) vs 1039 (393-2748) pmol/l h, p=0.052] than controls. Afro-Caribbean post-GDM women had lower glucose disappearance rate [1.3(0.6-2.8) vs 2.6 (1.8-3.8) 10(-2)/min, p=0.003] than controls, suggesting subtle glucose intolerance. CONCLUSIONS: Women with a history of GDM of three different ethnic groups, even in the presence of normal fasting glucose, display a range of metabolic abnormalities, including -cell dysfunction with variable insulin resistance. These derangements may be influenced by ethnicity.

Premature adrenarche leads to polycystic ovary syndrome? Long-term consequences.

Premature adrenarche is characterized by an early increase in adrenal androgen production that results in the development of pubic hair before the age of 8 years in girls and 9 years in boys, with or without axillary hair, and with no other signs of sexual development. Premature adrenarche has no adverse effects on the onset and progression of gonadarche and final height. However, it can no longer be considered a benign condition as it has been associated with hyperinsulinemia, dyslipidemia, and obesity already in the prepubertal period and polycystic ovary syndrome (PCOS) at adolescence. Furthermore, a possible association between premature adrenarche and metabolic and endocrine abnormalities with low birth weight has been postulated. PCOS, as recently redefined, is the most common endocrine disorder to affect women of reproductive age and has been associated with increased risk for type 2 diabetes and increased prevalence of cardiovascular risk factors at an earlier age than expected. Premature adrenarche and PCOS share similar metabolic disturbances. It may be that metabolic abnormalities start very early in life during the prenatal or prepubertal period and premature adrenarche may be a forerunner of PCOS and the metabolic syndrome in some girls. Large long-term epidemiological studies are needed to allow clear association of the two conditions and assessment of the risk of disease in later life.

Polycystic ovary syndrome. Revised diagnostic criteria and long-term health consequences.

The diagnostic criteria for polycystic ovary syndrome (PCOS) have recently been revised. The polycystic ovarian morphology has been introduced as part of the criteria and an international consensus has been achieved providing the basis for future research and collaboration. It is now accepted that polycystic ovary syndrome has important long-term health implications, including metabolic disorders and increased risk factors for cardiovascular disease. The overall risk of developing type 2 diabetes among women with PCOS was found to be increased 3-7 times. Women with PCOS have increased levels of cardiovascular risk factors: insulin resistance, obesity, dyslipidaemia, hypertension and markers of abnormal vascular function. However, the level of risk for cardiovascular disease remains uncertain. The limited epidemiological data available to date have shown no increase in cardiovascular events although the incidence of cerebrovascular events was increased. The evidence for an increased risk for endometrial carcinoma among women with PCOS is limited. Long-term epidemiological studies of women with well defined PCOS are needed in order to assess the risk of long-term health consequences, to identify the subgroups among PCOS women who need to be targeted and to determine the timing and nature of measures for intervention and prevention.

Ectopic thyroid tissue in the lower neck with a coexisting normally located multinodular goiter and brief literature review.

Ectopic thyroid tissue in the lower neck with a coexisting normally located multinodular goiter is a rare entity. We present a 27-year old asymptomatic woman with a recent history of a painless mass in the left side of her lower neck. Thyroid function tests were normal. An ultrasound of her neck showed a multinodular goiter and a 3.4 cm solid mass in the left lower cervical area. These findings were confirmed by an MRI scan of her neck. The Tc99m Pertechnetate scan showed the presence of a functioning area under the left lobe of the thyroid gland. The patient underwent surgery. The cervical mass was identified as a structure separate from the left lobe of the thyroid, without any attachments to the body of the gland and was uniformly resected. A subtotal thyroidectomy was also performed. The histology revealed that the separate structure represented ectopic thyroid tissue. The patient had an uneventful postoperative recovery, subsequent to which she was euthyroid and had normal calcium levels.

Delayed metabolic and thermogenic response to a mixed meal in normoglycemic European women with previous gestational diabetes.

We assessed postprandial thermogenesis (PPT) for 3 h following a mixed meal in 29 normoglycemic European women with previous gestational diabetes (GDM), compared with 37 control women. Given the potential role of catecholamines and insulin in the regulation of PPT, we assessed insulin and catecholamine responses to the meal. There was no significant difference between the two groups in resting energy expenditure, PPT (although lower in the GDM group), or catecholamine levels. However, we observed a difference in the shape of the PPT curve between groups, and by applying a mathematical model, there was a consistent delay in PPT, insulin, and noradrenaline responses to the meal in the GDM group (T: fitted time constant, geometric mean (95% confidence interval), T(PPT) 58 (47-72) vs. 42 (37-48) min, P = 0.006; T(ins) 32 (28-37) vs. 22 (19-27) min, P = 0.002; T(NA) 30 (23-38) vs. 18 (14-23) min, P = 0.01, respectively). Fidgeting activity during the study was assessed by a novel technique and was lower in the GDM group, resting [427 (381-477) vs. 511 (466-560) kJ/min, P = 0.02] but not postprandially. These delayed PPT, insulin, and noradrenaline responses to the meal in post-GDM women represent early metabolic changes. The decrease in fidgeting activity while resting, observed in the post-GDM group, may have physiological significance for energy balance.

Prevalence of polycystic ovaries in women with androgenic alopecia.

OBJECTIVE: Although androgenic alopecia is recognised to be a symptom of polycystic ovary syndrome (PCOS), it is not known whether polycystic ovaries (PCO) and associated endocrine abnormalities are present in patients who present with alopecia as a primary complaint. We therefore set out to determine the strength of the association between androgenic alopecia and PCO. We examined the prevalence of ultrasound-based polycystic ovarian morphology and associated clinical and biochemical features in a large multiethnic group of women whose presenting complaint was of alopecia, and in a control group. SUBJECTS AND METHODS: We studied 89 women of mixed ethnic origin with androgenic alopecia and compared them to 73 control women. A detailed history was taken, anthropometry was performed and assessment of body-hair distribution was made. The presence of PCO was established by pelvic ultrasound scan. Serum gonadotrophins, testosterone, androstenedione, dihydrotestosterone and sex hormone binding globulin concentrations were measured. RESULTS: Women with alopecia had a higher prevalence of PCO and hirsutism than the control population (PCO: 67% vs 27%, P<0.00001; hirsutism: 21% vs 4%, P=0.003). Women with alopecia (with or without PCO) had higher testosterone, androstenedione and free androgen index than controls, even though few had frankly abnormal androgens. CONCLUSIONS: These findings confirm an association between androgenic alopecia and PCO, and other symptoms of hyperandrogenaemia. Thus most women who present with androgenic alopecia as their primary complaint also have PCO and have indices of abnormal androgen production. Since PCO is a well known risk factor for development of type 2 diabetes, this association has important implications for long-term management.

Epidemiological characteristics of children with autoimmune thyroid disease.

OBJECTIVE: Chronic autoimmune thyroiditis (AT) is the most common cause of thyroid disease in children. The aim of the study was to define the epidemiological clinical and laboratory characteristics of children and adolescents with AT. DESIGN: Various parameters including thyroid ultrasonography of 228 children and adolescents aged 10.2 ± 2.5 yrs (mean ± SD) with AT, who attended our Pediatric Endocrine Unit during a 5-year period were retrospectively analysed. RESULTS: 191 (83.8%) were female and 142 (62.3%) were pubertal. At AT diagnosis, 130 children (57.0%) were euthyroid, 75 (32.9%) had subclinical hypothyroidism, 19 (8.3%) had hypothyroidism and 4 (1.8%) had hyperthyroidism. There was a positive correlation between thyroid stimulating hormone (TSH) levels and thyroid volume SDS (r=0.15, p=0.02). Sixty-three children (28%) had a goiter and 32 (14%) had thyroid nodules. Three children (1.3%) had papillary thyroid carcinoma. Compared to euthyroid children, children with hypothyroidism were younger (9.2 ± 1.8 vs 10.6 ± 2.4 yrs, p<0.05) and had higher thyroid volume SDS (3.1 ± 1.9 vs 1.2 ± 1.2, p<0.05) and higher prevalence of goiter [11(57.9%) vs 29(22.3%), p<0.05]. CONCLUSIONS: Children and adolescents with AT are mostly asymptomatic; the majority are female, pubertal and euthyroid. Hypothyroid children with AT have higher thyroid volume, higher prevalence of goiter and higher antithyroid antibodies titers compared to euthyroid children. Diagnosing AT at an early stage offers the opportunity for a timely intervention. The potential association of AT with papillary thyroid carcinoma is an additional reason for a careful follow-up of the patients with AT.

Elevation of soluble E-selectin levels following gestational diabetes is restricted to women with persistent abnormalities of glucose regulation.

OBJECTIVE: Increased levels of the soluble adhesion molecule sE-selectin have been reported in normoglycaemic women with previous gestational diabetes but not in other groups at increased risk of future type 2 diabetes. To explore the basis for these discrepant findings, we studied the relationship between sE-selectin and glucose regulation in a large group of women with previous gestational diabetes. DESIGN: Comparison of sE-selectin levels between a study cohort ascertained on the basis of recent gestational diabetes and suitable control subjects. PATIENTS: One hundred and forty women with recent gestational diabetes (104 European, 20 South Asian and 16 Afro-Caribbean) and 125 normoglycaemic control women (90 European, 19 South Asian and 16 Afro-Caribbean). MEASUREMENTS: sE-selectin, fasting lipids, insulin and current glucose regulation status. RESULTS: There was no overall difference in sE-selectin levels between women with a history of gestational diabetes and control women among the 3 ethnic groups. European post-GDM women with abnormal glucose regulation postpartum (n = 30) had higher sE-selectin than control women (67 (54-91) ng/ml vs. 57 (43-75) ng/ml, P = 0.049). There was no difference in sE-selectin between normoglycaemic European women with a history of gestational diabetes (n = 74) and control women, even though the former displayed metabolic abnormalities predictive of diabetes. In those European post-GDM women with normal glucose regulation postpartum, sE-selectin levels were negatively correlated with time since delivery (r = -0.25, P = 0.04), suggesting that the previously described elevation of sE-selectin following GDM pregnancies slowly resolves postpartum. There was no correlation between sE-selectin levels and features of insulin resistance. CONCLUSIONS: In contrast to previous findings, this larger study does not support a role for sE-selectin as a marker, independent of prevailing glucose levels, of early metabolic abnormalities or future diabetes risk in women with previous gestational diabetes.

Insulin resistance and beta-cell dysfunction in normoglycaemic European women with a history of gestational diabetes.

OBJECTIVE: Women with previous gestational diabetes (GDM) are at increased risk of subsequent type 2 diabetes. To characterize early metabolic abnormalities associated with this increased risk, we studied normoglycaemic women with a history of GDM. PATIENTS AND MEASUREMENTS: We performed an insulin-modified, frequently sampled intravenous glucose tolerance test (FSIVGTT) in 34 normoglycaemic European women with previous GDM and 44 European control women, deriving measures of insulin sensitivity, glucose effectiveness, glucose disappearance rate and acute insulin response to glucose. RESULTS: Post-GDM women were more obese than controls [body mass index (BMI), geometric mean (95% confidence interval); 25.3 kg/m2 (23.8-27.1 kg/m2) vs. 23.1 kg/m2 (21.9-24.3 kg/m2), P = 0.03]. Evidence of insulin resistance was provided by their lower insulin sensitivity as measured by FSIVGTT [0.6 x 10-4/min/pmol/l (0.3-1.2 x 10-4/min/pmol/l) vs. 1.5 x 10-4/min/pmol/l (1.2-1.8 x 10-4/min/pmol/l), P = 0.01] and by homeostatic model assessment [72% (49-107%) vs. 153% (113-206%), P = 0.004]; and by their higher fasting triglycerides [1.0 mmol/l (0.7-1.5 mmol/l) vs. 0.7 mmol/l (0.6-0.8 mmol/l), P = 0.001]. Though there was no difference between groups in fasting NEFA levels, acute NEFA suppression was diminished in the post-GDM group (P = 0.01). Concomitant beta-cell dysfunction in the post-GDM women was revealed by their lower disposition index [0.05/min (0.02-0.10/min) vs. 0.11/min (0.09-0.14/min), P = 0.02] compared to controls. The differences in insulin sensitivity, but not those of beta-cell function, were partly, though not completely, attributable to differences in regional and total adiposity. CONCLUSIONS: European normoglycaemic women with previous GDM display both glucoregulatory and antilipolytic insulin resistance, reduced beta-cell function and dyslipidaemia. These metabolic abnormalities are likely to contribute to their increased risk of future type 2 diabetes.