Food Cravings and Obesity in Women with Polycystic Ovary Syndrome: Pathophysiological and Therapeutic Considerations.

Polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age, constitutes a metabolic disorder frequently associated with obesity and insulin resistance (IR). Furthermore, women with PCOS often suffer from excessive anxiety and depression, elicited by low self-esteem due to obesity, acne, and hirsutism. These mood disorders are commonly associated with food cravings and binge eating. Hypothalamic signaling regulates appetite and satiety, deteriorating excessive food consumption. However, the hypothalamic function is incapable of compensating for surplus food in women with PCOS, leading to the aggravation of obesity and a vicious circle. Hyperandrogenism, IR, the reduced secretion of cholecystokinin postprandially, and leptin resistance defined by leptin receptors' knockout in the hypothalamus have been implicated in the pathogenesis of hypothalamic dysfunction and appetite dysregulation. Diet modifications, exercise, and psychological and medical interventions have been applied to alleviate food disorders, interrupting the vicious circle. Cognitive-behavioral intervention seems to be the mainstay of treatment, while the role of medical agents, such as GLP-1 analogs and naltrexone/bupropion, has emerged.

Two rare cases of benign struma ovarii with malignant recurrence.

Summary: Struma ovarii is an ovarian teratoma that comprises 2-5% of all ovarian teratomas. Malignant transformation of struma ovarii occurs in less than 5% of all cases, and metastatic disease is even rarer. We report two cases initially diagnosed with benign struma ovarii that presented malignant transformation, specifically highly differentiated follicular carcinoma of the ovary (HDFCO), some years after the first diagnosis. Case 1 concerns a 37-year-old female featuring HDFCO of the right ovary with multiple metastatic foci, who was diagnosed with benign struma ovarii 14 years ago. Case 2 concerns a 26-year-old female diagnosed with HDFCO of the left ovary. This patient was initially diagnosed with benign struma ovarii 6 years ago that recurred 4 years after the diagnosis. Both patients were treated with surgery, adjunctive total thyroidectomy, and radioactive iodine (131I) therapy. Learning points: Malignant transformation of struma ovarii is very rare (<5%). Diagnosis of HDFCO without extra ovarian dissemination is difficult due to the resemblance of its histological appearance with normal thyroid tissue. There is no consensus on the postoperative treatment of malignant struma ovarii (MSO). Clinical and histological features of MSO should be assessed for the postoperative treatment decisions. TSH suppression and thyroglobulin level measurements are necessary for patient follow-up.

Elevated FIB-4 Is Associated with Higher Rates of Cardiovascular Disease and Extrahepatic Cancer History in Patients with Type 2 Diabetes Mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is often complicated by steatotic liver disease, cardiovascular disease (CVD), and extrahepatic cancer. We investigated whether FIB-4, an indicator of liver fibrosis, is associated with a higher risk of CVD and extrahepatic cancer history in T2DM. METHODS: Two hundred and nine of 244 diabetics admitted to our center in one year were included and retrospectively evaluated. RESULTS: One hundred and fifty-two (72.7%) were males and 57 (27.3%) females. The mean age and FIB-4 were 64.3 ± 11 years, and 1.15 ± 0.5, respectively. One hundred and fifty patients (71.8%) had FIB-4 ≤ 1.3, and 59 (28.2%) had FIB-4 > 1.3. A history of CVD was presented in 76 (36.4%) patients, and of extrahepatic cancer in 39 (18.7%). Patients with CVD were significantly older than those without (68.4 ± 8.5 vs. 63.2 ± 11.5 years; p = 0.002), with significantly higher FIB-4 (1.26 ± 0.5 vs. 1.08 ± 0.5; p = 0.012). Patients with cancer were older, with higher FIB-4 compared to those without (68.2 ± 9.5 vs. 64.4 ± 10.9 years; p = 0.098 and 1.37 ± 0.6 vs. 1.1 ± 0.5; p = 0.004, respectively). FIB-4 > 1.3 was associated with a 2.1-fold probability for CVD (χ2 = 5.810; p = 0.025) and 2.7-fold probability for cancer history (χ2 = 7.603; p = 0.01). CONCLUSIONS: FIB-4 ≥ 1.3 is associated with a higher probability of CVD or extrahepatic cancer history. FIB-4 could potentially discriminate patients at risk, justifying stricter surveillance.

Diet, exercise, and supplements: what is their role in the management of the metabolic dysfunction-associated steatotic liver disease in children?

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as nonalcoholic fatty liver disease (NAFLD), is the main cause of chronic liver disease in children and adolescents. Indeed, epidemiological studies have shown that MASLD affects up to 40% of children with obesity. Despite the recent approval of medications that target weight loss in adolescents that could have benefits on pediatric MASLD, lifestyle interventions, such as diet and exercise, remain the mainstay of our therapeutic approach. More specifically, studies on diet alone have focused on the possible role of carbohydrate or fat restriction, albeit without a definite answer on the best approach. Weight loss after dietary intervention in children with obesity and MASLD has a beneficial effect, regardless of the diet used. In relation to the role of exercise in MASLD reversal, indirect evidence comes from studies showing that a sedentary lifestyle leading to poor fitness, and low muscle mass is associated with MASLD. However, research on the direct effect of exercise on MASLD in children is scarce. A combination of diet and exercise seems to be beneficial with several studies showing improvement in surrogate markers of MASLD, such as serum alanine aminotransferase and hepatic fat fraction, the latter evaluated with imaging studies. Several dietary supplements, such as vitamin E, probiotics, and omega-3 fatty acid supplements have also been studied in children and adolescents with MASLD, but with equivocal results. This review aims to critically present available data on the effects of lifestyle interventions, including diet, exercise, and dietary supplements, on pediatric MASLD, thus suggesting a frame for future research that could enhance our knowledge on pediatric MASLD management and optimize clinicians' approach to this vexing medical condition.

Early age at menarche and the risk of gestational diabetes mellitus: a cohort study.

PURPOSE: To evaluate whether there is an association between age at menarche (AAM) and the risk of gestational diabetes mellitus (GDM). METHODS: A retrospective cohort study was conducted, including 5390 pregnant women who were screened for GDM at Alexandra Hospital in Athens, Greece over a 15-year period (2000-2014). Maternal age, pre-pregnancy body mass index (BMI), height, family history of type 2 diabetes mellitus, parity, educational and smoking status, and AAM were recorded. The results were expressed as odds ratios (OR) with a 95% confidence interval (95% CI). RESULTS: Pregnant women with GDM experienced earlier menarche compared to normoglycemic women (12.9 ± 1.5 vs 13.1 ± 1.6, p < 0.001, respectively). The OR for a woman with AAM <12 years to develop GDM was 1.08 (95% CI 1.03-1.14), while the OR to be obese was 1.70 (95% CI 1.50-1.90). The multivariate logistic regression analysis showed that AAM is a risk factor for GDM. However, that effect was lost after adjusting for BMI. CONCLUSION: Early AAM may be associated with an increased risk of GDM. Therefore, it can be used to identify high-risk women and implement preconception interventions for GDM prevention. Future studies should be conducted to confirm these findings.

Nutrition of aging people with diabetes mellitus: Focus on sarcopenia.

As populations age, chronic diseases accumulate, and new health conditions emerge. One noteworthy pair that warrants further evaluation is diabetes mellitus and sarcopenia, given that the latter occurs in 28 % of the population aged over 50 who have diabetes mellitus. The management of both entails nutritional interventions, making the development of unified dietary recommendations an alluring strategy. This review aims to elucidate the current recommendations for the combined management of sarcopenia and diabetes, while featuring elements that require further research. The goal of nutritional management is to improve muscle mass and strength while regulating metabolic risk and glucose levels. To ensure muscle synthesis in the elderly, recommendations align at daily calorie intake that exceeds 30 kcal/kg, with adjustments based on comorbidities. Additionally, a protein intake of at least 1-1.2 g/kg/d is essential, emphasizing both daily and per-meal intake, and can be achieved through diet or branched-amino-acids supplements. Specific considerations for diabetes include restricted protein intake in diabetic nephropathy and exploring the potential link between branched amino acids and insulin resistance. Further recommendations that both promote metabolic health and have demonstrated at least a potential to increase muscle strength include prioritizing polyunsaturated fatty acids as a fat source and maintaining adequate levels of vitamin D. Clinicians should consult their patients on dietary optimization, but evidence is insufficient to recommend additional supplementation. Lastly, an emerging challenge of diabetes and sarcopenia is sarcopenic obesity, which requires the combination of a hypocaloric diet with increased protein intake.

Early onset type 2 diabetes mellitus: an update.

The incidence and prevalence of type 2 diabetes mellitus (T2DM) in young individuals (aged <40 years) have significantly increased in recent years, approximating two to threefold increase in the respective rates. Numerous risk factors including severe obesity, family history, ethnicity, maternal diabetes or gestational diabetes, and female sex contribute to a younger age of onset. In terms of pathogenesis, impaired insulin secretion is the key operating mechanism, alongside with ectopic adiposity-related insulin resistance. T2DM diagnosis in a young adult requires the exclusion of type 1 diabetes mellitus (T1DM), latent autoimmune diabetes of adults (LADA) and maturity-onset diabetes of the young (MODY). The establishment of such diagnosis is critical for prognosis, because early-onset T2DM is associated with rapid deterioration in pancreatic ß-cell secretory function leading to earlier initiation of insulin therapy. Furthermore, mortality and lifetime risk of developing complications, especially microvascular, is increased in these patients compared to both later-onset T2DM and T1DM patients; also, the latter are often developed earlier in the course of disease. The management of early-onset T2DM follows the same guidelines as in later-onset T2DM; yet patients aged 18-39 years are underrepresented in the big clinical trials on which the development of guidelines is based. Finally, young people with T2DM face significant challenges associated with social determinants, which compromise their adherence to therapy and induce diabetes distress. Future research focusing on the pathogenesis of ß-cell decline and complications, as well as on specific treatment shall lead to better understanding and management of early-onset T2DM.

Determinants of health-related quality of life of patients with type 2 diabetes and multimorbidity: a cross-sectional study.

PURPOSE: To examine the determinants of health-related quality of life (HRQoL) of patients with type 2 diabetes (PwD) and multimorbidity (MM) (at least one co-occurring condition besides T2D) among sociodemographic, disease-related, and MM variables and the association of MM with therapeutic targets. METHODS: A total of 179 PwD attending primary care (PC) in Greece answered the 15 dimension HRQoL (15D) questionnaire between August 2019 and October 2020. Sociodemographic, disease-related, and MM characteristics were recorded. MM was categorized as concordant or discordant based on whether or not it was related to the pathophysiology of T2D. Independent predictors of the 15D score were examined in stepwise regression models among sociodemographic, disease-related, and MM variables and the association of MM with glycated hemoglobin (A1C) and low-density lipoprotein cholesterol (LDL-C) was assessed. RESULTS: The mean 15D score was 0.85 ± 0.11 and the mean MM count was 4.3 ± 1.8. Significant predictors of a higher 15D score were male gender, married state, higher monthly income, and more physical activity. Significant predictors of a lower 15D score were employment, depression, musculoskeletal disease, coronary artery disease, neuropathy, and MM count, but discordant had a stronger effect than concordant MM. Increasing MM count was not significantly correlated with A1C and was correlated with lower LDL-C. CONCLUSION: Non-medical (physical activity and sociodemographic) rather than disease-related characteristics and discordant more than concordant co-occurring conditions affected HRQoL of multimorbid PwD who did not have worse (A1C) or achieved better (LDL-C) therapeutic targets. A generalist approach to the non-medical needs and overall health conditions of PwD could be promoted in PC within the social determinants of health and MM.

Menopausal Hormone Therapy in Women with Type 2 Diabetes Mellitus: An Updated Review.

Menopause is accompanied by several metabolic adaptations, which are related to insulin resistance, increased total body fat mass, and central abdominal fat accumulation, predisposing women to type 2 diabetes mellitus (T2DM) development. Metabolic syndrome has a high prevalence in postmenopausal women, indicating the loss of estrogen protection on metabolic and cardiovascular health. Moreover, earlier age at menopause has been related to increased risk of T2DM. Menopausal hormone therapy (MHT) has favorable results in glucose metabolism. Indeed, it reduces the risk of T2DM in women without this condition and improves glycemic control in women with T2DM. Before MHT initiation in women with clinical indications, it is imperative to assess their cardiovascular disease (CVD) risk, using official electronic algorithms for score calculation. The latter will determine regimen, dose, and administration route of MHT. Oral estrogens are preferable in women with low CVD risk, while transdermal administration is indicated in those with moderate and high CVD risk, as the risk of stroke and venous thromboembolism (VTE) is increased with oral administration. Oral 17ß-estradiol is usually preferred in women with T2DM, as this route has more beneficial effects on glucose metabolism. Oral estrogens are also suggested in perimenopausal or recently postmenopausal women with low CVD risk. Although oral estrogens have favorable effects when indicated, the risk of VTE or stroke should always be considered. Micronized progesterone, dydrogesterone, and transdermal norethisterone are the progestogens used in postmenopausal women with T2DM and intact uterus. MHT should not be initiated in women > 60 years or > 10 years in menopause, as there is an increased thromboembolic risk in women with established atherosclerosis and no additional cardiovascular benefit in women without atherosclerosis. In conclusion, MHT administration in postmenopausal women with T2DM can be safe and effective as long as the therapeutic regimen has been properly selected according to their cardiovascular, metabolic, and fracture risk.

Thyroid disorders induced by immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) are a revolutionary class of drugs that powerfully contribute to cancer therapy by harnessing the immune system to fight malignancies. However, their successful use as anti-cancer drugs is accompanied by a wide spectrum of immune-related adverse effects (irAEs), including endocrinopathies. Among them, thyroid dysfunction stands out as one of the most common endocrinopathies induced by ICI therapy and surfaces as a prominent concern. Destructive thyroiditis is the pathophysiological basis shared by the most common patterns of thyrotoxicosis followed by hypothyroidism and isolated hypothyroidism. Diagnostic approach is guided by clinical manifestation, laboratory evaluation and imaging modalities. Treatment approaches range from the substitution of levothyroxine to the utilization of beta blockers, depending on the extent of thyroid dysfunction's severity. While the medical community is dealing with the evolution and complexities of immunotherapy, recognizing and effectively managing ICI-induced thyroid dysfunction emerged as crucial for enhancing patient safety and achieving improved outcomes. The aim of this review is to navigate the significance of ICI-induced thyroid dysfunction unraveling the various patterns, underlying mechanisms, diagnostic approaches, and treatment strategies. It, also, highlights the impact of various factors such as cancer subtype, ICI dosage, age, and genetic susceptibility on the risk of experiencing dysfunction.

Gonadal dysfunction in women with diabetes mellitus.

It is well known that both type 1 and type 2 diabetes mellitus (DM) are related to increased risk for cardiovascular (CV) and chronic kidney disease (CKD). However, besides these prominently presented complications, DM has also been associated with reproductive dysfunctions. It seems that these disorders are met in up to 40% of women with DM and consist of delayed menarche, all types of menstrual disorders, such as amenorrhea, oligomenorrhea, menstrual irregularity, as well as menorrhagia, infertility, characteristics of polycystic ovary syndrome (PCOS) and early (or rarely late) menopause. In type 1 DM (T1DM), insulin treatment, although it has reduced the rates of insulinopenic-induced hypogonadotropic hypogonadism, an entity commonly presented in many women with the disease in the past decades, when it is used in excess it can also promote hyperandrogenism. Regarding type 2 DM (T2DM), insulin resistance (IR) and hyperinsulinemia have mainly been implicated in the pathogenesis of reproductive dysfunctions, as insulin can act as gonadotropin on the theca cells of the ovary and can lead to hyperandrogenism and inhibition of proper ovulation. This review aims to detail the reproductive dysfunctions associated with DM and provide scientific data to enlighten the underlying pathogenetic mechanisms.

The Role of the Glycemic Index and Glycemic Load in the Dietary Approach of Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is a common metabolic disorder that often develops during pregnancy, characterized by glucose intolerance and insulin resistance (IR). To ensure the well-being of both the mother and the fetus, the body undergoes multiple metabolic and immunological changes that result in peripheral IR and, under certain hereditary or acquired abnormalities, GDM in predisposed women. The adverse short- and long-term effects of GDM impact both the mother and the fetus. Nutrition seems to play an important role to prevent GDM or improve its evolution. An emphasis has been given to the proportion of carbohydrates (CHO) relative to protein and lipids, as well as dietary patterns, in GDM. The effects of CHO on postprandial glucose concentrations are reflected in the glycemic index (GI) and glycemic load (GL). Diets rich in GI and GL may induce or exacerbate IR, whereas diets low in GI and GL appear to enhance insulin sensitivity and improve glycemic control. These positive outcomes may be attributed to direct interactions with insulin and glucose homeostasis or indirect effects through improved body composition and weight management. This comprehensive narrative review aims to explore the significance of nutrition, with a focus on the critical evaluation of GI and GL in the dietary management of women with GDM.

Statin use and incident type 2 diabetes mellitus in women after menopause.

Menopause is associated with adverse cardiometabolic changes which increase the risk of new-onset type 2 diabetes (T2DM) and cardiovascular disease (CVD). Statins are widely used for primary and secondary CVD prevention, given their beneficial effects on the lipid profile and the vessel wall. On the other hand, statins increase the risk of T2DM. This association has been evaluated mainly in mixed-gender studies, without gender-specific evaluation. This narrative review evaluates the use of statins and the related risk of new-onset T2DM among postmenopausal women. Studies that incorporated a gender-specific analysis report a higher risk of new-onset T2DM in women than in men on treatment with statins. Fewer studies evaluated female-only samples; these confirm the observed association between statin use and new-onset T2DM. Factors influencing the association between statin use and T2DM include the type and dose of statin and the baseline metabolic status. Women may benefit from stratification of their metabolic risk before initiating a statin for CVD prevention.

Sleep disorders during pregnancy: an underestimated risk factor for gestational diabetes mellitus.

Sleep disorders are highly prevalent during pregnancy and significantly affect women's health and quality of life. Gestational diabetes mellitus (GDM) is one of the most common metabolic complications during pregnancy and constitutes a significant risk factor for both mother and fetus in the short and the long term. While the association between sleep disorders and type 2 diabetes mellitus (T2DM) is indisputable, it is not clear whether there is a link between sleep disorders and GDM. The aim of this article was to investigate the association between sleep disorders and GDM and whether the treatment of sleep disorders may prevent GDM development. Insomnia, obstructive sleep apnea (OSA), restless legs syndrome (RLS), and narcolepsy were the most common sleep disorders identified during pregnancy and were related to poor sleep quality and short or prolonged sleep duration. They were all associated with an increased risk of GDM. The ideal sleep duration for pregnant women was determined at 8-9 h daily. In conclusion, sleep disorders constitute a risk factor for GDM. It is imperative that prospective studies be conducted to evaluate the effect of the early management of sleep disorders on GDM manifestation and control. Healthcare providers should highlight the importance of sufficient sleep to reinforce pregnancy outcomes.

Efficacy and safety of metformin during pregnancy: an update.

During the last decades, gestational diabetes mellitus (GDM) prevalence has been on the rise. While insulin remains the gold standard treatment for GDM, metformin use during pregnancy is controversial. This review aimed to comprehensively assess the available data on the efficacy and safety of metformin during pregnancy, both for the mother and the offspring. Metformin has been validated for maternal efficacy and safety, achieving comparable glycemic control with insulin. Additionally, it reduces maternal weight gain and possibly the occurrence of hypertensive disorders. During the early neonatal period, metformin administration does not increase the risk of congenital anomalies or other major adverse effects, including lower APGAR score at 5 min, neonatal intensive care unit admissions, and respiratory distress syndrome. Several studies have demonstrated a reduction in neonatal hypoglycemia. Metformin has been associated with an increase in preterm births and lower birth weight, although this effect is controversial and depends on the indication for which it was administered. Evidence indicates possible altered fetal programming and predisposition to childhood obesity and metabolic syndrome during adulthood after use of metformin in pregnancy. With critical questions still requiring a final verdict, ongoing research on the field must be conducted.

Cardiac disease in Cushing's syndrome. Emphasis on the role of cardiovascular magnetic resonance imaging.

BACKGROUND: Cushing's Syndrome (CS) is associated with increased cardiovascular morbidity and mortality. In endogenous CS, cardiovascular mortality remains increased for up to 15 years post remission of hypercortisolism. Similarly, patients with exogenous CS have 4-fold increased incidence of cardiovascular events, regardless of pre-existing cardiovascular disease (CVD). OBJECTIVE: To present the pathophysiology, prognosis, clinical and imaging phenotype of cardiac disease in CS. METHODS: A Pubmed search for cardiac disease in CS over the last 20 years was conducted using combinations of relevant terms. Preclinical and clinical studies, as well as review papers reporting on subclinical heart failure (HF), cardiomyopathy, coronary heart disease (CHD), and cardiovascular imaging were selected. RESULTS: Cardiac disease in CS is associated with direct mineralocorticoid and glucocorticoid receptor activation, increased responsiveness to angiotensin II, ectopic epicardial adiposity, arterial stiffness and endothelial dysfunction, as well as with diabetes mellitus, hypertension, hyperlipidemia, obesity and prothrombotic diathesis. Subclinical HF and cardiomyopathy are principally related to direct glucocorticoid (GC) effects and markedly improve or regress post hypercortisolism remission. In contrast, CHD is related to both direct GC effects and CS comorbidities and persists post cure. In patients without clinical evidence of CVD, echocardiography and cardiac magnetic resonance (CMR) imaging reveal left ventricular hypertrophy, fibrosis, diastolic and systolic dysfunction, with the latter being underestimated by echocardiography. Finally, coronary microvascular disease is encountered in one third of cases. CONCLUSION: Cardiovascular imaging is crucial in evaluation of cardiac involvement in CS. CMR superiority in terms of reproducibility, operator independency, unrestricted field of view and capability of tissue characterisation makes this modality ideal for future studies.

The Thyroid-cardiac Axis: Thyroid Function, Cardiac Rhythmology, and Sudden Cardiac Death.

It is well known that thyroid dysfunction increases the risk of cardiovascular mortality and morbidity. The pleiotropic effect of thyroid hormones has a profound effect on the cardiovascular system, influencing both the formation of a normal cardiac rhythm and rhythm disturbance. A number of research studies have demonstrated correlations between TSH and FT4 levels and significant cardiovascular events. The pathophysiological mechanisms underlying these complex associations are, however, inadequately defined. A system-based examination of the relationship between thyroid homeostasis and cardiovascular disease could pave the way for novel study areas and a more individualised strategy for the management of individuals at cardiovascular risk.

Comparison of treatment with insulin detemir and NPH in women with gestational diabetes mellitus: glycemic control and pregnancy outcomes. A retrospective study.

PURPOSE: The objective of this retrospective study was to compare glycemic control, pregnancy outcomes, and neonatal outcomes in women with gestational diabetes mellitus (GDM) treated with (a) insulin detemir and (b) insulin neutral protamine Hagedorn (NPH). METHODS: A total of 192 women with GDM were included in the analysis. Ninety-eight women received detemir, while 94 women received NPH. Data regarding medical history, glycemic control, and time and mode of delivery, as well as neonatal outcomes, were recorded. RESULTS: Baseline characteristics were comparable between the two groups. There were no differences with respect to the week of insulin initiation, total insulin dose, duration of insulin therapy, daily insulin dose/weight in early and late pregnancy, or the number of insulin injections per day. Maternal overall weight gain during pregnancy and weight gain per week did not differ either. The detemir group had slightly lower HbA1c levels at the end of gestation [median: det 5.2% (33 mmol/mol) vs NPH 5.4% (36 mmol/mol), p=0.035). There were no cases of hypoglycemia or allergic reactions in the two groups. There were also no differences regarding neonatal outcomes according to the available data, given that data in some cases were missing. CONCLUSION: The use of insulin detemir was found to be equally effective and safe compared to NPH in women with GDM.

Secondary diabetes mellitus in pheochromocytomas and paragangliomas.

Secondary diabetes mellitus (DM) in secretory pheochromocytomas and paragangliomas (PPGLs) is encountered in up to 50% of cases, with its presentation ranging from mild, insulin resistant forms to profound insulin deficiency states, such as diabetic ketoacidosis and hyperglycemic hyperosmolar state. PPGLs represent hypermetabolic states, in which adrenaline and noradrenaline induce insulin resistance in target tissues characterized by aerobic glycolysis, excessive lipolysis, altered adipokine expression, subclinical inflammation, as well as enhanced gluconeogenesis and glucogenolysis. These effects are mediated both directly, upon adrenergic receptor stimulation, and indirectly, via increased glucagon secretion. Impaired insulin secretion is the principal pathogenetic mechanism of secondary DM in this setting; yet, this is relevant for tumors with adrenergic phenotype, arising from direct inhibitory actions in beta pancreatic cells and incretin effect impairment. In contrast, insulin secretion might be enhanced in tumors with noradrenergic phenotype. This dimorphic effect might correspond to two distinct glycemic phenotypes, with predominant insulin resistance and insulin deficiency respectively. Secondary DM improves substantially post-surgery, with up to 80% remission rate. The fact that surgical treatment of PPGLs restores insulin sensitivity and secretion at greater extent compared to alpha and beta blockade, implies the existence of further, non-adrenergic mechanisms, possibly involving other hormonal co-secretion by these tumors. DM management in PPGLs is scarcely studied. The efficacy and safety of newer anti-diabetic medications, such as glucagon-like peptide 1 receptor agonists and sodium glucose cotransporter 2 inhibitors (SGLT2is), as well as potential disease-modifying roles of metformin and SGLT2is warrant further investigation in future studies.