Learning Points • Sex hormone binding globulin (SHBG) concentration associates with insulin-resistance. • We looked at the relation between baseline SHBG concentration and future glycaemic status over an up to 10-year period, for women who were normoglycaemic at baseline. • In multiple linear regression analysis, a lower SHBG was associated with a higher fasting glucose independent of age and index of multiple deprivation. • These findings suggest that a low SHBG level, at a relatively young age is a risk marker for future impaired glucose handling in women. Precis: In a laboratory study, we found that low sex hormone-binding globulin level is a risk marker for future relative dysglycaemia in women, with index of multiple deprivation also an independent predictor of future prediabetes/type 2 diabetes mellitus.Editor, Previous work has suggested that a low sex hormone-binding globulin (SHBG) concentration associates with insulin resistance [1]. We previously showed that a low circulating SHBG level (<30 nmol/L) is associated with the presence of the metabolic syndrome in a multiethnic population [2] with lower levels found in both men and women of Pakistan ethnic origin compared with Caucasian and African-Caribbean origin people. In that study SHBG correlated positively with insulin sensitivity as estimated by HOMA-S [3] and negatively with waist-hip ratio, BMI and DBP across all ethnic groups, whereas in multivariate logistic regression analysis a low SHBG increased the likelihood of the metabolic syndrome being present. Furthermore, SHBG levels are often lower in women with polycystic ovarian syndrome (PCOS) [4–6]. There is therefore the potential for SHBG, given its relative ease of measurement (commonly by automated immunoassay), not requiring fasting status or special processing to have utility in identifying people at increased risk or developing impaired glucose handling in the future. In the light of this, we looked at the predictive value of SHBG in relation to the future development of impaired glucose handling in women in a preliminary study in 115 women, over an up to 10-year period. The women were normoglycaemic at baseline. Outcome was either fasting glucose or glycosylated haemoglobin (HbA1c) [7], as measures of glycaemia. 'As anonymised data were used for the analysis from a laboratory database and no patient was contacted in this study, approval was sought and obtained from the Research and Innovation team'. The mean age of the women at the start of follow-up was 26.8 years (SD, 9.0; range, 16–65). Over the up to 10-year follow-up period, 6% developed non-diabetic hyperglycaemia (defined as HbA1c 42–47 mmol/mol) to and 1% type 2 diabetes (T2DM, defined as HbA1c ≥48 mmol/mol). In multiple linear regression analysis, a lower SHBG was associated with higher fasting glucose [normalised beta (β) −0.22; P = 0.02] independent of age (β 0.28; P = 0.01) and index of multiple deprivation (IMD) (β −0.11; P = 0.06) and South Asian ethnicity (β −0.13; P = 0.04). In logistic regression, we found that age was predictive of subsequent development of prediabetes/T2DM [odds ratio 1.08 (95% CI, 1.02–1.15); P = 0.01] independent of IMD/SHBG/ethnicity. In the light of these results, we suggest that a low SHBG level may have value as a risk marker for the development of future glucose dysregulation in women, with age also an independent predictor of nondiabetic hyperglycaemia/T2DM. Where someone has been found to have a low SHBG, there is the potential for targeted lifestyle measures to be implemented to prevent or delay the onset of glucose dysregulation. In our study, a younger age profile of the group likely influenced the low cumulative incidence of T2DM over the 10-year follow-up period. Nevertheless, SHBG may prove to be a useful future marker for the impact of lifestyle change programmes to reduce metabolic risk those people found to have a low SHBG, including women with PCOS. We plan further work to improve our understanding of this and to continue to follow-up this cohort of women in the coming years. Acknowledgements Conflicts of interest There are no conflicts of interest.
Early weight gain following initiation of antipsychotic treatment predicts longer-term weight gain, with attendant long-term consequences including premature cardiovascular events/death. An important question is whether there is a difference in weight change over time between people with affective versus nonaffective psychosis. Here we describe the results of a real-world analysis of the BMI change in the months postdiagnosis with affective versus nonaffective psychosis.We undertook an anonymised search across one Primary Care Network in Cheshire, UK with a total population of 32 301 individuals. We reviewed the health records of anyone who had been diagnosed over a 10-year period between June 2012 and June 2022 for the first time with first episode nonaffective psychosis versus psychosis associated with depression or bipolar affective disorder (affective psychosis).The overall % change in BMI was +8% in nonaffective psychosis individuals and +4% in those with a diagnosis of affective psychosis - however, the distribution was markedly skewed for nonaffective psychosis patients. Using caseness as >30% increase in BMI; affective = 4% cases and nonaffective = 13% cases, there was a three-fold difference in terms of increase in BMI. In regression analysis, the r2 linking the initial BMI to % change in BMI was 0.13 for nonaffective psychosis and 0.14 for affective psychosis.The differences observed here in the distribution of weight change over time between individuals with affective versus nonaffective psychosis may relate to underlying constitutional differences. The phenotypic and genetic factors underlying this difference remain to be defined.
Objective. Hormone replacement therapy (HRT) in postmenopausal women is controversial, with an elevated cardiovascular event rate for combined estrogen–progestogen but no adverse cardiovascular effect and possible cumulative benefit for estrogen alone. Here we measured the effects of differing estrogen/progestogen combinations on the insulin-like growth factor (IGF)/IGF binding protein (IGFBP) system which has been implicated in the pathophysiological mechanisms underlying cardiovascular disease, higher IGFBP-1 levels having been linked with a reduced cardiovascular risk.Design. Oral conjugated equine estrogens (CEE) alone, or in combination with the increasingly androgenic progestogens medroxyprogesterone acetate, desogestrel or norethisterone, were given in a randomized triple crossover fashion to 35 healthy postmenopausal women. Serum concentrations of IGFs and the principal circulating IGFBPs were measured.Results. Circulating IGF-I, IGFBP-3 and IGF-I/IGFBP-3 molar ratio were significantly reduced by CEE. These effects were reversed by progestogens according to their androgenicity. Plasma IGFBP-1 concentration increased from baseline to CEE alone. This rise was opposed by progestogens of increasing androgenicity. IGFBP-2 levels fell and IGFBP-4 increased with CEE, with no further change with addition of progestogens. CEE increased the proportional contribution of IGFBP-1 and IGFBP-4 to total IGFBP binding and decreased the IGFBP-3 contribution. This was reversed by progestogens.Conclusion. There are marked changes in molar ratios of the IGFBPs in relation to estrogen/progestogens in HRT. The effect of progestogens on IGF bioavailability could be an important determinant of the longer-term risks of specific HRT preparations by opposing the potentially beneficial effects of CEE alone on cardiovascular risk.
Background Lithium is viewed as the first-line long-term treatment for prevention of relapse in people with bipolar disorder. Aims This study examined factors associated with the likelihood of maintaining serum lithium levels within the recommended range and explored whether the monitoring interval could be extended in some cases. Method We included 46 555 lithium rest requests in 3371 individuals over 7 years from three UK centres. Using lithium results in four categories (<0.4 mmol/L; 0.40–0.79 mmol/L; 0.80–0.99 mmol/L; ≥1.0 mmol/L), we determined the proportion of instances where lithium results remained stable or switched category on subsequent testing, considering the effects of age, duration of lithium therapy and testing history. Results For tests within the recommended range (0.40–0.99 mmol/L categories), 84.5% of subsequent tests remained within this range. Overall, 3 monthly testing was associated with 90% of lithium results remaining within range, compared with 85% at 6 monthly intervals. In cases where the lithium level in the previous 12 months was on target (0.40–0.79 mmol/L; British National Formulary/National Institute for Health and Care Excellence criteria), 90% remained within the target range at 6 months. Neither age nor duration of lithium therapy had any significant effect on lithium level stability. Levels within the 0.80–0.99 mmol/L category were linked to a higher probability of moving to the ≥1.0 mmol/L category (10%) compared with those in the 0.4–0.79 mmol/L group (2%), irrespective of testing frequency. Conclusion We propose that for those who achieve 12 months of lithium tests within the 0.40–0.79 mmol/L range, the interval between tests could increase to 6 months, irrespective of age. Where lithium levels are 0.80–0.99 mmol/L, the test interval should remain at 3 months. This could reduce lithium test numbers by 15% and costs by ~$0.4 m p.a.
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