Lifestyle intervention in individuals with impaired glucose regulation affects Caveolin-1 expression and DNA methylation.

AIMS: We investigated whether a lifestyle intervention could influence expression and DNA methylation of diabetes-related genes in patients with impaired glucose regulation (IGR), the results were compared to bariatric surgery, considering it an intensive change. METHODS: Twenty participants with IGR had adipose tissue biopsy and blood collected pre- and post-lifestyle (6 months) intervention; 12 obese patients had subcutaneous fat taken before and after bariatric surgery. RNA/DNA was extracted from all samples and underwent qPCR. DNA was bisulphite converted and 12 CpG sites of Caveolin-1 (CAV1) promoter were pyrosequenced. RESULTS: lifestyle intervention resulted in opposite direction changes in fat tissue and blood for CAV1 expression and DNA methylation and these changes were correlated between tissues, while no significative differences were found in CAV1 expression after bariatric surgery. CONCLUSIONS: Our findings suggest a role for CAV1 in modulating adipocyte function as a consequence of lifestyle changes, as exercises and diet. These results may provide insights into new therapeutic targets for diabetes prevention.

Screening for Hypogonadism in Primary Healthcare: How to do this Effectively.

BACKGROUND: Testosterone, the most important androgen produced by the testes, plays an integral role in male health. Testosterone levels are increasingly being checked in primary healthcare as awareness of the risks of male hypogonadism grows. AIM: To investigate what tests are performed to screen for hypogonadism and to exclude secondary hypogonadism. DESIGN AND SETTING: All participants attended general practices in the UK. METHODS: Data search was performed using the EMIS®: clinical database (provider of the majority of GP operating systems in Cheshire). The anonymised records of male patients aged 18-98 years who had undergone a check of serum testosterone during a 10-year period were analysed. RESULTS: Overall screening rate was 4.3%. Of 8 788 men with a testosterone result, 1 924 men (21.9%) had a total testosterone level <10 nmol/L. Just 689 of 8 788 men (7.8%) had a sex hormone-binding globulin (SHBG) result, corresponding to 30.5% of those potentially hypogonadal. Estimated free testosterone was negatively associated with BMI (Spearman's rho -0.2, p<0.001) as was total testosterone in the over 50 s. Of 1 924 potentially hypogonadal men with a serum testosterone <10 nmol/L, 588 of 1 924 (30.6%) had a check of serum prolactin. 46.3% and 41.7% had LH and FSH measured, respectively. Only 19.1% of 1 924 men with a hypogonadal total testosterone level were subsequently put on testosterone replacement. The percentage of men in the relatively socially disadvantaged category was similar for both eugonadal and hypogonadal men with a much higher rate of screening for hypogonadism in more socially advantaged men. CONCLUSIONS: Screening in primary healthcare identified a significant minority of men who had potential hypogonadism. Interpretation of a low serum testosterone requires measurement of serum prolactin, LH and FSH in order to rule out secondary hypogonadism. We suggest that this becomes part of routine screening with a balanced screening approach across the socioeconomic spectrum.

Polycystic ovarian syndrome: Assessment of approaches to diagnosis and cardiometabolic monitoring in UK primary care.

INTRODUCTION: Polycystic ovarian syndrome (PCOS) is one of the commonest endocrine disorders affecting women of reproductive age. We examined the specific tests that are done in primary care to lead to the diagnosis of PCOS, and to support the diagnosis once made. METHODS: One thousand seven hundred and ninety-seven women were identified from a pooled GP practice database. The search included all patients defined with PCOS or related terms. Records included demographic information, medical history (diagnoses), blood test results and whether a pelvic ultrasound scan had been performed. RESULTS: The most common age of PCOS diagnosis was 20-29 years; 67.7% of the women had at least one concomitant Read-coded diagnosis. Most pelvic ultrasound scans were performed in the month immediately prior to diagnosis. In the 12 months prior to the diagnosis of PCOS being made, 30.5% of women underwent a measurement of their serum total testosterone level while 29.6% had their serum SHBG measured. For serum oestradiol, the corresponding statistics were 28.4%, LH 45.3% and for FSH 45.5% checked before diagnosis. Fasting blood glucose, random glucose and HbA1c were checked in 10.2%, 18.8% and 4.2%, of women before diagnosis, respectively, but in only 7.9%, 6.0% and 3.4% of women in the 24 months after diagnosis. There was a tendency for endocrine testing (oestradiol, LH, FSH, testosterone, SHBG) to peak in the weeks before diagnosis. For plasma glucose, testing was performed more evenly over time as for serum cholesterol. Of all women diagnosed with PCOS, 32.8% were prescribed metformin, 3.7% antihypertensives, 2.2% statins and 63.5% an oestrogen-containing contraceptive pill or HRT. CONCLUSION: The underlying pathophysiology of PCOS is still not fully understood. As a result, treatment is often focused on individual symptoms, not the syndrome itself. Robust laboratory led protocols would provide the necessary information to enable an appropriate diagnostic evaluation/cardometabolic monitoring.