The association of vasomotor symptoms with fracture risk and bone mineral density in postmenopausal women: a systematic review and meta-analysis of observational studies.

BACKGROUND/AIMS: Vasomotor symptoms (VMS) adversely affect postmenopausal quality of life. However, their association with bone health has not been elucidated. This study aimed to systematically review and meta-analyze the evidence regarding the association of VMS with fracture risk and bone mineral density (BMD) in peri- and postmenopausal women. METHODS: A literature search was conducted in PubMed, Scopus and Cochrane databases until 31 August 2023. Fracture, low BMD (osteoporosis/osteopenia) and mean change in lumbar spine (LS) and femoral neck (FN) BMD were assessed. The results are presented as odds ratio (OR) and mean difference (MD), respectively, with a 95% confidence interval (95% CI). The I2 index quantified heterogeneity. RESULTS: Twenty studies were included in the qualitative and 12 in the quantitative analysis (n=49,659). No difference in fractures between women with and without VMS was found (n=5, OR 1.04, 95% CI 0.93-1.16, I2 16%). However, VMS were associated with low BMD (n=5, OR 1.54, 95% CI 1.42-1.67, I2 0%). This difference was evident for LS (MD -0.019 g/cm2, 95% CI -0.03 to -0.008, I2 85.2%), but not for FN BMD (MD -0.010 g/cm2, 95% CI -0.021 to 0.001, I2 78.2%). These results were independent of VMS severity, age and study design. When the analysis was confined to studies that excluded menopausal hormone therapy use, the association with BMD remained significant. CONCLUSIONS: The presence of VMS is associated with low BMD in postmenopausal women, although it does not seem to increase fracture risk.

Physical signs and atherosclerotic cardiovascular disease in familial hypercholesterolemia: the HELLAS-FH Registry.

AIMS: Three physical signs, namely tendon xanthomas, corneal arcus and xanthelasma, have been associated with heterozygous familial hypercholesterolemia (heFH). The prevalence and clinical significance of these signs are not well established among contemporary heFH individuals. This study explored the frequency as well as the association of these physical signs with prevalent atherosclerotic cardiovascular disease (ASCVD) in heFH individuals. METHODS: Data from the Hellenic Familial Hypercholesterolemia Registry were applied for this analysis. The diagnosis of heFH was based on the Dutch Lipid Clinic Network Score. Multivariate logistic regression analysis was conducted to examine the association of heFH-related physical signs with prevalent ASCVD. RESULTS: Adult patients ( n  = 2156, mean age 50 ±â€Š15 years, 47.7% women) were included in this analysis. Among them, 14.5% had at least one heFH-related physical sign present. The prevalence of corneal arcus before the age of 45 years was 6.6%, tendon xanthomas 5.3%, and xanthelasmas 5.8%. Among physical signs, only the presence of corneal arcus before the age of 45 years was independently associated with the presence of premature coronary artery disease (CAD). No association of any physical sign with total CAD, stroke or peripheral artery disease was found. Patients with physical signs were more likely to receive higher intensity statin therapy and dual lipid-lowering therapy, but only a minority reached optimal lipid targets. CONCLUSION: The prevalence of physical signs is relatively low in contemporary heFH patients. The presence of corneal arcus before the age of 45 years is independently associated with premature CAD.

Obesity and atherosclerotic cardiovascular disease in adults with heterozygous familial hypercholesterolemia: An analysis from HELLAS-FH registry.

BACKGROUND: Familial hypercholesterolemia (FH) and obesity are well-established risk factors of atherosclerotic cardiovascular disease (ASCVD). Despite high prevalence, their joint association with ASCVD remains largely unknown. OBJECTIVE: To investigate the association of obesity with prevalent ASCVD in individuals with heterozygous FH (HeFH) enrolled in the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH). METHODS: FH diagnosis was based on Dutch Lipid Clinic Network (DLCN) criteria. Adults with at least possible FH diagnosis (DLCN score ≥3) and available body mass index (BMI) values were included. Homozygous FH individuals were excluded. RESULTS: 1655 HeFH adults (mean age 51.0 ± 14.4 years, 48.6% female) were included; 378 (22.8%) and 430 (26.0%) were diagnosed with probable and definite FH, respectively. Furthermore, 371 participants (22.4%) had obesity and 761 (46.0%) were overweight. Prevalence of ASCVD risk factors increased progressively with BMI. Prevalence of coronary artery disease (CAD) was 23.4% (3.2% for stroke and 2.7% for peripheral artery disease, PAD), and increased progressively across BMI groups. After adjusting for traditional ASCVD risk factors and lipid-lowering medication, individuals with obesity had higher odds of established CAD (OR: 1.54, 95% CI: 1.04-2.27, p = 0.036) as well as premature CAD (OR: 1.74, 95% CI: 1.17-2.60, p = 0.009) compared with those with normal BMI. No association was found with stroke or PAD. CONCLUSIONS: Over half of adults with HeFH have overweight or obesity. Obesity was independently associated with increased prevalence of CAD in this population.

Hyperparathyroidism and Peripheral Arterial Disease.

Primary hyperparathyroidism (PHPT) is presented in various forms, including classic PHPT, characterised by increased parathyroid hormone (PTH) secretion, normohormonal PHPT, and normocalcaemic PHPT. Secondary hyperparathyroidism is characterised by increased PTH secretion triggered by factors such as vitamin D deficiency and kidney failure. This review aims to discuss the involvement of hyperparathyroidism (HPT) in atherosclerosis, including peripheral arterial disease (PAD). The increased level of PTH is involved in developing subclinical and overt vascular diseases, encompassing endothelial dysfunction, vascular stiffness, hypertension, and coronary and peripheral arterial diseases. It has been consistently associated with an augmented risk of cardiovascular morbidity and mortality, independent of classical risk factors for atherosclerosis. Chronic hypercalcemia associated with increased levels of PTH contributes to the development of calcification of vessel walls and atherosclerotic plaques. Vascular calcification can occur in the intima or media of the arterial wall and is associated with stiffness of peripheral arteries, which the formation of atherosclerotic plaques and narrowing of the vessel lumen can follow. For treating hyperparathyroidism, particularly SHPT, calcimimetics, novel phosphorus binders and novel vitamin D receptor activators are used. However, they are ineffective in severe PHPT. Therefore, parathyroidectomy remains the primary therapeutic option of PHPT.

Antiosteoporosis therapy after discontinuation of menopausal hormone therapy: a systematic review.

OBJECTIVE: Menopausal hormone therapy (MHT) has consistently shown a bone protective effect by reducing the risk of vertebral, non-vertebral, and hip fractures in postmenopausal women regardless of baseline fracture risk. However, the optimal sequential treatment after MHT discontinuation has not been determined. This systematic review aimed to obtain the best evidence regarding the effect of antiresorptive or osteoanabolic treatment on bone mineral density (BMD) and/or fracture risk following MHT. METHODS: A comprehensive search was conducted in the PubMed, Scopus, and Cochrane databases up to October 31, 2023. Randomized-controlled trials (RCTs) and observational studies conducted in postmenopausal women were included. RESULTS: After the exclusion of duplicates, 717 studies were identified. Two were eligible for qualitative analysis, one RCT and one retrospective cohort study. The RCT showed that alendronate 10 mg/day for 12 months further increased lumbar spine (LS) BMD by 2.3% following MHT and maintained femoral neck (FN) BMD in postmenopausal women (n = 144). It also decreased bone anabolic and resorption markers by 47 and 36%, respectively. In the retrospective study (n = 34), raloxifene 60 mg/day increased both LS and FN BMD at 12 months by 3 and 2.9%, respectively. No fractures were reported. CONCLUSIONS: Antiresorptive therapy with either a bisphosphonate (i.e., alendronate) or raloxifene could be considered a sequential antiosteoporosis therapy after MHT withdrawal since they have been shown in studies to further increase BMD. However, no safe conclusions can be drawn from the existing literature.

Familial Hypercholesterolemia in the Elderly: An Analysis of Clinical Profile and Atherosclerotic Cardiovascular Disease Burden from the Hellas-FH Registry.

BACKGROUND: Familial hypercholesterolemia (FH) carries a high risk of atherosclerotic cardiovascular disease (ASCVD). As the population ages, the age-related influence on clinical characteristics and outcomes becomes increasingly pertinent. This cross-sectional analysis from the HELLAS-FH registry aims to explore potential differences in clinical characteristics, treatment, ASCVD, and goal achievement between those younger and older than 65 years with FH. RESULTS: A total of 2273 adults with heterozygous FH (51.4% males) were studied. Elderly FH patients (n = 349) had a higher prevalence of ASCVD risk factors, such as hypertension (52.1% vs. 20.9%, p < 0.05) and type 2 diabetes (16.9% vs. 6.0%, p < 0.05), compared to younger patients (n = 1924). They also had a higher prevalence of established ASCVD (38.4% vs. 23.1%, p < 0.001), particularly CAD (33.0% vs. 20.2%, p < 0.001), even after adjusting for major ASCVD risk factors. Elderly patients were more frequently and intensively receiving lipid-lowering treatment than younger ones. Although post-treatment LDL-C levels were lower in elderly than younger patients (125 vs. 146 mg/dL, p < 0.05), both groups had similar attainment of the LDL-C target (3.7% vs. 3.0%). CONCLUSIONS: Elderly FH patients have a higher prevalence of ASCVD, particularly CAD. Despite more aggressive treatment, the achievement of LDL-C targets remains very poor. These results emphasize the importance of early FH diagnosis and treatment in reducing ASCVD.

Cardiovascular health and the menopause, metabolic health.

Estrogen depletion following menopause predisposes to increased risk of cardiovascular disease (CVD), mainly due to ischemic heart disease. This is mostly evident in cases with premature menopause. The pathophysiological basis for this atherosclerotic process is the accumulation of several risk factors, such as abdominal obesity, atherogenic dyslipidemia, insulin resistance and arterial hypertension. The presence of vasomotor symptoms may further augment this risk, especially in women younger than 60 years. Menopausal hormone therapy (MHT) exerts many beneficial effects on lipid profile and glucose homeostasis as well as direct arterial effects, and may reduce CVD risk if initiated promptly (i.e.,<60 years or within ten years of the final menstrual period). Transdermal estradiol and micronized progesterone or dydrogesterone are the safest regimens in terms of venous thromboembolic events (VTE) and breast cancer risk. In any case, an individualized approach, taking into account the patient's total CVD, VTE and breast cancer risk, is recommended.

Thyroid Disorders and Peripheral Arterial Disease.

Hypothyroidism and hyperthyroidism, both overt and subclinical, are associated with increased risk of cardiovascular morbidity and mortality. The association between thyroid-stimulating hormone levels and cardiovascular risk has been demonstrated in large epidemiological studies and meta-analyses and is now considered a U-shaped curve. Several pathophysiological mechanisms linking thyroid and cardiovascular disease are known; however, specific clinical complications of peripheral arterial disease as endpoints of clinical trials have not been adequately investigated. The potential mechanisms linking hypothyroidism and peripheral arterial disease are endothelial dysfunction, blood pressure changes, dyslipidemia, and low-grade systemic inflammation. The potential mechanisms linking hyperthyroidism and peripheral arterial disease are hyperdynamic circulation, elevated systolic blood pressure, hypercoagulability, and possibly increased arterial inflammation.

Comparative Effectiveness of Therapeutic Interventions in Pregnancy and Lactation-Associated Osteoporosis: A Systematic Review and Meta-analysis.

CONTEXT: The optimal management of pregnancy and lactation-associated osteoporosis (PLO) has not been designated. OBJECTIVE: To systematically review the best available evidence regarding the effect of different therapeutic interventions on bone mineral density (BMD) and risk of fractures in these patients. METHODS: A comprehensive search was conducted in PubMed/Scopus databases until December 20, 2022. Data were expressed as weighted mean difference (WMD) with 95% CI. The I2 index was employed for heterogeneity. Studies conducted in women with PLO who received any antiosteoporosis therapy were included. Studies including women with secondary causes of osteoporosis or with transient osteoporosis of the hip were excluded. Data extraction was independently completed by 2 researchers. RESULTS: Sixty-six studies were included in the qualitative analysis (n = 451 [follow-up time range 6-264 months; age range 19-42 years]). The increase in lumbar spine (LS) BMD with calcium/vitamin D (CaD), bisphosphonates, and teriparatide was 2.0% to 7.5%, 5.0% to 41.5%, and 8.0% to 24.4% at 12 months, and 11.0% to 12.2%, 10.2% to 171.9%, and 24.1% to 32.9% at 24 months, respectively. Femoral neck (FN) BMD increased by 6.1% with CaD, and by 0.7% to 18% and 8.4% to 18.6% with bisphosphonates and teriparatide (18-24 months), respectively. Meta-analysis was performed for 2 interventional studies only. Teriparatide induced a greater increase in LS and FN BMD than CaD (WMD 11.5%, 95% CI 4.9-18.0%, I2 50.9%, and 5.4%, 95% CI 1.2-9.6%, I2 8.1%, respectively). CONCLUSION: Due to high heterogeneity and lack of robust comparative data, no safe conclusions can be made regarding the optimal therapeutic intervention in women with PLO.

Familial hypercholesterolemia and its manifestations: Practical considerations for general practitioners.

Familial hypercholesterolemia (FH) is the most common genetic disorder of lipid metabolism, affecting almost 1 in 250 individuals worldwide. It is usually inherited via the autosomal dominant way and is characterized by aberrantly high total and low-density lipoprotein cholesterol (LDL-C) concentrations from early childhood, predisposing to increased risk of premature atherosclerotic cardiovascular disease (ASCVD), mostly coronary heart disease (CHD). Despite its high prevalence in the general population and the high ASCVD risk, FH is often underdiagnosed and undertreated. Genetic diagnosis is not always necessary since specific criteria, taking into account the patient's individual and family history, clinical signs, and untreated LDL-C concentrations, may be used for prompt diagnosis. Except for CHD, which may be already evident at diagnosis, leading to increased mortality, other non-CHD morbidities, such as stroke, peripheral artery disease, carotid artery stenosis, and aortic valve calcification may be also present, substantiating the need for prompt intervention. Statins constitute the mainstay of treatment both in adults and children >8 years old. In cases of statin intolerance or not achieving the LDL-C target despite maximally tolerated statin dose, ezetimibe and/or proprotein convertase subtilisin-kexin type 9 inhibitors may be used. The advent of recently approved medications, such as inclisiran and bempedoic acid, either as monotherapy or as add-on therapy to statins, has further enhanced the therapeutic armamentarium that can be used in FH patients. The purpose of this narrative review is to provide practical considerations regarding the diagnostic and therapeutic approach to FH patients.

The Effect of Menopause and Menopausal Hormone Therapy on the Risk of Peripheral Artery Disease.

Peripheral artery disease (PAD), defined as lower extremity arterial disease, constitutes an underestimated aspect of the menopause-associated risk of atherosclerotic cardiovascular disease (ASCVD). Accumulation of ASCVD risk factors, such as atherogenic dyslipidaemia, diabetes, and arterial hypertension, after the transition to menopause may contribute to atherosclerotic plaque formation in peripheral arteries. However, inconsistency exists among studies as to whether transition to menopause increases the risk of PAD, although early menopause (<45 years) or premature ovarian insufficiency may accelerate peripheral atherosclerotic plaque formation. Menopausal hormone therapy may decrease the risk of PAD if administered early (i.e., within the first 5-6 years after last menstruation), whereas it has no effect in women with established ASCVD.

Cardiometabolic Risk, Peripheral Arterial Disease and Cardiovascular Events in Polycystic Ovary Syndrome: Time to Implement Systematic Screening and Update the Management.

Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine disorder in women of reproductive age. It presents with gynaecologic, metabolic, and psychologic manifestations. The dominant drivers of pathophysiology are hyperandrogenism and insulin resistance. Both conditions are related to cardiometabolic risk factors, such as obesity, hypertension, dyslipidaemia, hyperglycaemia, type 2 and gestational diabetes, nonalcoholic fatty liver disease and obstructive sleep apnoea. Women with PCOS of reproductive age consistently demonstrated an elevated risk of subclinical atherosclerosis, as indicated by different measurement methods, while findings for menopausal age groups exhibited mixed results. Translation of subclinical atherosclerosis into the increased incidence of peripheral arterial disease and major cardiovascular (CV) events is less clear. Although several expert groups have advised screening, the CV risk assessment and prevention of CV events are frequently underdiagnosed and overlooked aspects of the management of PCOS. A combination of lifestyle management and pharmacotherapy, including the promising new era of anti-obesity medicine, can lead to improvements in cardiometabolic health.

Testosterone and Peripheral Arterial Disease.

Testosterone levels in men begin declining in the early years of adulthood, with a 1-2% reduction/year. Low testosterone levels in men are associated with obesity, metabolic syndrome, diabetes mellitus, dyslipidaemia, hypertension and increased cardiovascular mortality. However, observational studies of testosterone levels in males and their relationship with peripheral arterial disease (PAD) have yielded mixed results; only some cohorts show a clear association with low free testosterone levels. This discrepancy may, in part, be due to methodological issues with estimating free testosterone but also to different effects of testosterone on the vessel wall and metabolism. While testosterone improves glycaemic control, has anti-obesity effects and induces vasodilation, it also stimulates platelet aggregation and increases the haematocrit. Androgen deprivation treatment for advanced prostate cancer may be associated with elevated cardiovascular risk, as is testosterone abuse for performance enhancement. On the other hand, judicious treatment of male hypogonadism or testosterone treatment of trans-men appears to be safe.

Early menopause and premature ovarian insufficiency are associated with increased risk of dementia: A systematic review and meta-analysis of observational studies.

BACKGROUND/AIMS: Among other risk factors, the decline in estrogen concentrations during menopause may compromise cognitive function. Whether early menopause (EM) is associated with an increased risk of dementia remains unclear. The purpose of this study was to systematically review and meta-analyze current evidence regarding the association between EM or premature ovarian insufficiency (POI) and the risk of dementia of any type. MATERIALS AND METHODS: A comprehensive literature search was conducted through the PubMed, Scopus and CENTRAL databases up to August 2022. Study quality was assessed using the Newcastle-Ottawa scale. Associations were calculated as odds ratio (OR) with 95 % confidence interval (CI). The I2 index was employed for heterogeneity. RESULTS: Eleven studies (nine assessed as of good and two as of fair quality) were included in the meta-analysis (n = 4,716,862). Women with EM demonstrated a greater risk of dementia of any type than women of normal age at menopause (OR 1.37, 95 % CI 1.22-1.54; I2 93%). However, after excluding a large retrospective cohort study, the results were altered (OR 1.07, 95 % CI 0.78-1.48; I2 94%). Increased risk of dementia was also found in women with POI (OR 1.18, 95 % CI 1.15-1.21; I2 0%). Subgroup analysis showed that this risk was mostly evident in cohort studies, and those which included women with natural menopause. CONCLUSIONS: Women with EM or POI may be at increased risk of dementia compared with women of normal age at menopause, but further research investigating that hypothesis is warranted.

The clinical significance of low dose biotin supplements (<300µg/day) in the treatment of patients with hypothyroidism: crucial or overestimated?

BACKGROUND: In the last decade, the combination of the widespread use of streptavidin-biotin technology and biotin-containing supplements (BCS) in the daily clinical practice, have led to numerous reports of erroneous hormone immunoassay results. However, there are no studies assessing the clinical and biochemical significance of that phenomenon, when treating patients with hypothyroidism. Therefore, a prospective study was designed to investigate the potential alterations in the measurement of thyroid hormone concentrations and clinical consequences in patients with hypothyroidism using low -dose BCS containing less than 300 µg/day. METHODS: Fifty-seven patients on thyroxine supplementation, as a result of hypothyroidism and concurrent use of BCS at a dose <300µg/day for 10 to 60 days were prospectively evaluated. Namely, TSH and free T4 (FT4) concentration measurements were performed, during BC supplementation and 10 days post BCS discontinuation and compared to 31 age-matched patients with supplemented hypothyroidism and without BCS. RESULTS: A statistically significant increase in TSH and decline in FT4 concentrations was observed after BCS discontinuation. However, on clinical grounds, these modifications were minor and led to medication dose adjustment in only 2/57 patients (3.51%) in whom TSH was notably decreased after supplement discontinuation. CONCLUSION: Our study suggests that changes in thyroid hormones profiling, due to supplements containing low dose biotin, are of minimal clinical relevance and in most cases don't occult the need to adjust the thyroxine replacement dose in patients with hypothyroidism. Larger, well-designed trials are required to further evaluate this phenomenon.

Female Papillary Thyroid Cancer Survivors Are at Increased Risk of Adenomyosis and Endometrial Hyperplasia.

PURPOSE: Thyroid cancer (TC) is the most common endocrine cancer worldwide, affecting mainly women of reproductive age. However, no data exist about its association with endometrial or uterine disorders. This study aimed to assess the risk of hyperproliferative pathology of the reproductive system in female ТС survivors. METHODS: This was a cross-sectional study of female patients aged 20-45 years diagnosed with papillary TC (PTC) from 1994-2018. Age-matched females with normal thyroid structures served as controls. RESULTS: One hundred and sixteen patients (mean age 36.7±61 years) and 90 age-matched controls were included. PTC survivors demonstrated an increased risk for adenomyosis [odds ratio (OR) 2.5, 95% confidence interval (CI) 1.3-4.8] and endometrial hyperplasia (OR 3.9, 95% CI 1.1-14.3), compared with controls. The risk for adenomyosis was higher after the ten post-operative years (OR 5.3, 95% CI 2.29- 12.05) than during the first 5-10 years (OR 2.3, 95% CI 1.02-5.10) and increased with the number of RAI courses and the degree of TSH suppression. The risk of endometrial hyperplasia was most evident during the first five years post-thyroidectomy (OR 6.0, 95% CI 1.4-25.5), especially in patients with TSH <0.1 mU/L (OR 6.8, 95% CI 1.4-33.28) No difference in uterine leiomyomas or endometrial polyps was found between PTC survivors and controls. CONCLUSIONS: Female PTC survivors are at increased risk of endometrial hyperplasia and adenomyosis compared with those with normal thyroid structures.

Early menopause and premature ovarian insufficiency may increase the risk of sarcopenia: A systematic review and meta-analysis.

PURPOSE: Menopausal transition, resulting from a decline in estrogen concentrations, may compromise musculoskeletal health. However, it is unclear if early menopause (defined as age at menopause <45 years) and premature ovarian insufficiency (defined as age at menopause <40 years) are associated with increased risk of sarcopenia. The aim of this systematic review and meta-analysis was to synthesize studies evaluating the association between age at menopause and risk of sarcopenia. METHODS: A comprehensive search was conducted in PubMed, CENTRAL and Scopus, up to 31 December 2022. Data were expressed as standardized mean difference with 95 % confidence intervals. The I2 index was employed to evaluate heterogeneity. RESULTS: Six studies were included in the qualitative and quantitative analysis, with a total of 18,291 post-menopausal women. Compared with women of normal age at menopause (>45 years), women with early menopause demonstrated lower muscle mass, assessed by appendicular skeletal muscle mass/body mass index [standardized mean difference (SMD) -0.14, 95 % confidence interval (CI) -0.20 to -0.07, p < 0.001; I2 0%]. However, no differences in muscle strength, assessed by handgrip strength (SMD -0.15, 95 % CI -0.31 to 0.01, p = 0.071; I2 72%), and muscle performance, assessed by gait speed (SMD -0.11, 95 % CI -0.29 to 0.05, p = 0.18; I2 79%), were found. Women with premature ovarian insufficiency had lower handgrip strength (SMD -0.3, 95 % CI -0.58 to -0.01, p = 0.04; I2 74.6 %) and gait speed (SMD -0.13, 95 % CI -0.23 to -0.04, p = 0.004; I2 0%) compared with women of normal age at menopause. CONCLUSION: Early menopause is associated with reduced muscle mass and premature ovarian insufficiency with reduced muscle strength and performance compared with normal age at menopause.

Assessment of Type 2 Diabetes Risk in Young Women with Polycystic Ovary Syndrome.

Women with polycystic ovary syndrome (PCOS) are at increased risk for dysglycemia and type 2 diabetes compared to healthy BMI-matched women of reproductive age: robust evidence exists supporting this notion. The presence of altered glycemic status in young women with the syndrome presents a distinct challenge for the clinician for several reasons. Firstly, the reported incidence of this disorder varies among the limited available studies. Furthermore, there is a lack of consensus on the best screening method, which women to screen, at what frequency, and which strategies need to be implemented to reduce the above risk. We provide data regarding the prevalence of dysglycemia in young women suffering from PCOS and the pathophysiological mechanisms underlying the disorder. In addition, we present evidence suggesting universal screening with the oral glucose tolerance test in young women with the syndrome, irrespective of age or BMI status, to identify and manage glycemic abnormalities in a timely manner. Regarding follow-up, oral glucose testing should be carried out at regular intervals if there are initial abnormal findings or predisposing factors. Finally, the efficacy of a well-balanced diet in conjunction with regular exercise and the use of non-pharmacologic agents in this specific population is discussed.