Background and Aims Type 2 diabetes mellitus (T2DM) is the leading global cause of end-stage kidney disease (ESRD). Patients receiving hemodialysis often have a high cardiometabolic risk profile, including insulin resistance, glycemic variability, chronic inflammation, sarcopenia, and altered mineral metabolism. In this setting, standard glycemic markers are often unreliable, supporting the use of additional non-pharmacological strategies, particularly structured physical activity, alongside standard treatment. This narrative review synthesizes current evidence on metabolic dysregulation in hemodialysis patients with T2DM and evaluates the potential role of intradialytic exercise as a multi-target intervention. Methods A focused narrative search was conducted in PubMed, Scopus and Web of Science (2014–2025). Randomized trials, observational studies, clinical guidelines and narrative reviews addressing key metabolic and musculoskeletal complications, CKD-MBD, and intradialytic exercise in advanced kidney disease were considered. Conclusions Intradialytic exercise represents a feasible adjunct strategy targeting interconnected metabolic pathways in patients with T2DM and ESRD. Further large-scale prospective studies are warranted to define the optimal intensity, modality and timing of intradialytic exercise and to clarify its long-term cardiometabolic and clinical benefits.
Objective Evidence on advanced hybrid closed-loop (AHCL) systems in older adults with type 1 diabetes (T1D) remains limited. This study compared the effectiveness and safety of the MiniMed 780G system between adults aged ≥60 years and younger adults. Methods We conducted a cross-sectional study in patients with T1D using the MiniMed 780G system. Eligible participants were aged ≥40 years and had used the device for at least four weeks before study entry. Clinical variables, body composition, grip strength, and glycemic outcomes were compared according to age group (<60 vs. ≥60 years). Results A total of 118 patients were included, 45% of whom were aged ≥60 years. In this group, 79% were independent for basic activities of daily living and 60% used SmartGuard at optimal settings. Glycemic management was similar in both age groups, including time in range (76.58±8.59 vs. 76.73±9.58; p=0.535), time in tight range (52.0±10.02 vs. 52.75±10.73; p=0.694), and time below range <70 mg/dL (1.39±1.33 vs. 1.81±1.39; p=0.100). In adjusted ANCOVA models, age group was not significantly associated with either TIR or TITR. Optimal SmartGuard settings, grip strength, fat mass, and phase angle were more strongly associated with glycemic profile than age. Conclusions MiniMed 780G use was safe and effective in older adults with T1D, achieving glycemic outcomes comparable to younger adults. Optimal SmartGuard settings are associated with a better metabolic profile and should be considered regardless of age. Additionally, grip strength and body composition should be included in the clinical assessment of patients with T1D using AHCL systems.
Background:A knowledge gap persists regarding whether virtual training differs from in-person training in terms of metabolic control and clinical safety among adults with type 1 diabetes mellitus (T1D) initiating the MiniMed™ 780G advanced hybrid closed-loop (AHCL) system. Methods:Observational study comparing two retrospective cohorts of adult patients with type 1 diabetes mellitus (T1DM) treated with the Medtronic MiniMed™780G hybrid closed-loop insulin automation system: one cohort trained in-person and a second cohort trained virtually at the Hospital Universitario San Ignacio, Bogotá (Colombia). Metabolic control and safety parameters were evaluated 12 weeks after training initiation. A logistic regression model was developed to identify factors associated with meeting glycemic target (Time in range 70-180 mg/dL ≥ 70%) at 12 weeks. Results:191 patients were analyzed; (49.7% virtual 50.3% in-person training). After 12 weeks, no statistically significant differences were observed in TIR between the cohorts (75% vs. 77.5%, p = 0.51). Severe hypoglycemia (<54 mg/dL) decreased significantly in both groups (p<0.02), without differences between cohorts. The type of training was not significantly associated with achieving the goals of TIR (adjusted OR 0.78; 95% CI:0.16-3.82; p=0.76). Younger age (<45 years) was independently associated with improved metabolic control (adjusted OR 0.08; 95% CI:0.01-0.75; p=0.02). Higher socioeconomic status showed a trend toward better outcomes (adjusted OR 35.04; 95% CI:0.94-1260.6; p=0.05). Conclusions:Both virtual and in-person training are effective and safe strategies for initiating the MiniMed™ 780G AHCL system in adults with T1D, with no significant differences between training modalities.
Immune checkpoint inhibitors (ICIs) are increasingly used in oncology and commonly cause thyroid dysfunction. Most patients who develop hypothyroidism after ICI-induced thyroiditis respond to standard weight-based levothyroxine replacement. However, causes of treatment-refractory hypothyroidism are less well recognized in this context. We describe an 81-year-old woman with uterine cancer treated with lenvatinib and pembrolizumab who developed ICI-related thyroiditis with subsequent hypothyroidism. Despite progressive levothyroxine dose escalation to nearly twice the expected weight-based dose, thyroid-stimulating hormone (TSH) remained elevated after normalization of free thyroxine (FT4) and triiodothyronine (T3). Evaluation for malabsorption and nonadherence was unrevealing. Further investigation identified significant proteinuria associated with lenvatinib therapy. Given that thyroid hormone circulates primarily bound to plasma proteins, urinary loss of protein-bound thyroid hormone was suspected to contribute to the increased levothyroxine requirement. Following temporary discontinuation and subsequent dose reduction of lenvatinib, proteinuria improved and thyroid function tests (TFTs) normalized, allowing for a reduction in levothyroxine dose. This case highlights that excessive proteinuria can lead to urinary loss of protein-bound thyroid hormone, resulting in apparent levothyroxine resistance. Clinicians should consider renal losses along with gastrointestinal and medication-related causes when thyroid hormone requirements exceed expected dosing. This is particularly relevant in patients receiving combination cancer therapies that increasingly include ICIs.
Background The accuracy of the FreeStyle Libre 2 system in critically ill patients needing insulin therapy remains inadequately evaluated. Objective To evaluate the clinical and numerical accuracy of continuous glucose monitoring (FreeStyle Libre 2) and capillary glucometry (StatStrip) compared with central laboratory glucose in critically ill patients requiring insulin therapy. Methods We conducted a diagnostic accuracy study, evaluating simultaneously two index tests, the FreeStyle Libre 2 and capillary glucose, compared to the central laboratory glucose (venous or arterial) as reference standard. The study included critically ill adult patients admitted to the intensive care unit (ICU) with diabetes or stress hyperglycemia, requiring insulin therapy, and ventilatory or vasopressor support. Numerical accuracy was assessed using ISO 15197:2013 criteria and Mean Absolute Relative Difference (MARD). Clinical accuracy was evaluated using Clarke and Parkes error grid analysis. Results A total of 157 paired measurements were collected. FreeStyle Libre 2 showed a MARD comparable to capillary glucose (10.43% vs 7.58%; p=0.14). Neither method met ISO 15197:2013 numerical accuracy criteria. In the clinical accuracy analysis, FreeStyle Libre 2 classified 100% of measurements within zones A+B on both the Clarke and Parkes grids, whereas capillary glucose achieved 97.6% and 100%, respectively. Conclusions FreeStyle Libre 2 showed numerical accuracy comparable to capillary blood glucose and consistently reliable clinical performance in critically ill patients needing insulin therapy. These results support its potential as an alternative to capillary glucose monitoring in the ICU. More studies involving a greater number of hypoglycaemic events are required to confirm its effectiveness in this critical range.
Immune checkpoint inhibitors (ICIs) offer important clinical benefits in antitumor therapy. However, they may cause potential and unpredictable immune-related adverse events (irAEs) due to the non-specific immunity activation. Although adrenocortical insufficiency (AI) is a rare irAE, rapid identification and treatment can help patients avoid life-threatening cortisol crises. We describe the case of a 60-year-old Chinese male patient with liver cancer who developed intractable hyponatremia, fatigue, and loss of appetite three months after completing treatment with cadonilimab. Intravenous rehydration and symptomatic treatment were ineffective. The diagnosis of ICI-induced secondary AI was confirmed after refinement of cortisol levels and adrenocorticotropic hormone (ACTH). Additionally, mild subclinical hypothyroidism was identified as a concurrent endocrine finding. Electrolyte disturbances and general malaise improved markedly after oral administration of exogenous cortisol hormone. This case supports existing evidence regarding ICI-related secondary AI and highlights the importance of timely endocrine evaluation in patients with persistent hyponatremia and non-specific systemic symptoms.
Background: COVID-19, caused by SARS-CoV-2, affects multiple organ systems, including the thyroid gland. Non-Thyroidal Illness Syndrome (NTIS) is frequently observed in severe systemic disease. NTIS-like thyroid hormone alterations have previously been reported in COVID-19. However, the relationship between these changes and disease outcomes remains unclear. Objectives: We aimed to evaluate thyroid function and vitamin D concentrations in hospitalized COVID-19 patients, and to analyze the association between hormonal measurements and patient characteristics with COVID-19 mortality. Methods: We conducted a retrospective database search of 846 adult patients hospitalized in a dedicated COVID-19 hospital at the peak of the pandemic. Based on the availability of serum levels of TSH, FT3, FT4, and vitamin D, 137 patients were included in the analysis. Descriptive statistics, comparative analyses, and logistic regression were used to evaluate the associations of laboratory measurements, sex, and age with COVID-19 mortality. Results: Decreased thyroid hormone and vitamin D concentrations were more common than in the general population, although none differed between deceased and COVID-19 survivors. Among the cohort, 63.5% had decreased TSH, 21.2% had decreased FT3, 24.1% had decreased FT4, and 75.9% presented with vitamin D deficiency. Comparative analyses showed no significant differences in TSH ( P = .82), FT3 ( P = .40), FT4 ( P = .81), or vitamin D ( P = .78) levels between deceased and surviving patients. Deceased patients were older than survivors (median [IQR]: 75.5 [71.0-80.8] vs 71.0 [61.0-77.0] years; P = .002), with age emerging as the only predictor of mortality (OR = 1.07, 95%CI: 1.02-1.11; P = .001; all other variables P > .33). Conclusions: NTIS-like thyroid hormone alterations and vitamin D deficiency are highly prevalent among hospitalized COVID-19 patients but do not predict in-hospital mortality. Age remains the major risk factor for death in this population. Our findings confirm that COVID-19 frequently affects the endocrine system and highlight the need for further research on long-term thyroid outcomes.
Clitoromegaly in a newborn with otherwise typically appearing female genitalia indicates exposure to excess androgens in fetal life. Congenital Adrenal Hyperplasia (CAH) is the most common cause of virilization at birth and empiric treatment is often pursued due to the risk of life-threatening adrenal crisis. Turner syndrome (TS) does not usually present with atypical genital appearance or other signs of hyperandrogenism, unless Y chromosome material is present. In this report, we describe a newborn who was noted to have clitoromegaly soon after birth with an otherwise normal exam and no syndromic features. Empiric treatment with hydrocortisone and fludrocortisone was started while initial laboratory results were pending. However, prior to receiving CAH hormonal panel results, karyotype testing returned as [45,XO(3)/46,XX(17)], consistent with mosaic TS. Testing for Y chromosome material, pursued as a potential cause of clitoromegaly, was negative. To add to the diagnostic dilemma, newborn screening for CAH was also negative. Results from the CAH panel done soon after birth eventually returned and revealed an elevated 17-hydroxyprogesterone level (17-OHP) of 1540 ng/dl, which is more congruent with non-classical CAH and does not typically result in clitoromegaly at birth. To clarify the diagnosis, a 250 mcg cosyntropin stimulation test was performed after holding steroids for a week. Post-stimulation 17-OHP of 82334 ng/dL confirmed classical CAH secondary to 21-hydroxylase deficiency and genetic analysis identified biallelic pathogenic deletions of CYP21A2 gene. Current TS guidelines recommend testing for Y chromosome material if masculinizing features develop. This case underlines the value of including CAH in the differential diagnosis as another potential cause of virilization in patients with TS. The concurrence of CAH and TS poses added complexity for clinical management due to their overlapping impacts on linear growth, puberty, reproductive function, bone density and metabolic health.
The XLH Matters 2024 GCC Edition meeting convened 51 physicians from 6 Gulf countries to discuss the diagnosis and management of patients with X-linked hypophosphatemia (XLH). This was the first XLH Matters meeting held in the Gulf Cooperation Council (GCC) region, reflecting the unique healthcare structure, cultural context, and patient needs. The key themes of the meeting included: challenges faced by GCC clinicians in diagnosing and treating XLH, the importance of multi-disciplinary care, the psychosocial impact, and the principles of effective transition of patients from pediatric to adult care. Participants emphasized the importance of raising awareness of XLH among primary care physicians, pediatricians, and dentists to facilitate early diagnosis in the region. Genetic testing was highlighted as the key tool supporting diagnosis, but wider access to this is needed across the GCC. A structural, progressive, and personalized model for pediatric-to-adult transition was proposed, based on the individual needs of the patient and including patient empowerment and continuity of care. The meeting underscored the need for regional collaboration, awareness initiatives, and implementation of recent clinical guidelines to improve outcomes for people with XLH in the GCC region.
Metformin-associated gastrointestinal (GI) intolerance is a frequent clinical problem that can limit treatment initiation, delay dose escalation, and reduce long-term adherence in patients with type 2 diabetes mellitus. Common symptoms include nausea, diarrhea, abdominal discomfort, and bloating, although symptom pattern and severity vary substantially between individuals. This narrative review summarizes current evidence on the determinants, mechanisms, and clinical evaluation of metformin-associated GI intolerance. In routine practice, assessment should begin with potentially modifiable exposure-related factors, including dose, single-dose burden, titration pace, formulation, administration with meals, kidney function, and concomitant medications. If symptoms persist or appear disproportionate to treatment exposure, clinicians should then consider broader host susceptibility, including baseline GI vulnerability, microbiome-related influences, altered bile acid handling, mucosal and neuroregulatory responses, comorbidity burden, and polypharmacy. This exposure–susceptibility framework provides a practical way to interpret metformin-related GI symptoms in routine care. It supports a stepwise clinical approach in which modifiable contributors are addressed first, broader context is reviewed when needed, and premature discontinuation is avoided whenever possible. Despite limitations in the current evidence base, available data support a structured and clinically useful approach to metformin intolerance.
Background: Romosozumab is an anabolic agent approved for the treatment of severe osteoporosis in postmenopausal women and in men at high risk of fracture. However, real-world data on its effectiveness, particularly in patients with diabetes mellitus (DM) or prior exposure to antiresorptive therapy, remain limited. Methods: Adult patients (⩾18 years) who received romosozumab between January 2021 and May 2024 and had both baseline and post-treatment dual-energy X-ray absorptiometry (DEXA) scans were included. Bone mineral density (BMD) at the lumbar spine, total hip and femoral neck was assessed before and after 12 months of therapy. Subgroup analyses were undertaken according to diabetes status and previous antiresorptive therapy exposure. Results: Eighty-seven patients were included (mean age 66.7 ± 13.0 years; 94.3% female). The median percentage increase in lumbar spine BMD was 6.7% (IQR 1.3-12.6), while increases at the total hip and femoral neck were 2.9% (IQR −1.1 to 9.1) and 2.3% (IQR −3.9 to 9.7), respectively. Patients without diabetes demonstrated significantly greater BMD gains than those with diabetes at the lumbar spine (9.9% vs 3.1%; P = .020), total hip (4.1% vs 0.3%; P = .027), and femoral neck (3.9% vs 0.1%; P = .028). Similarly, treatment-naïve patients had greater improvements in total hip BMD compared with those with prior antiresorptive exposure (8.3% vs 2.2%; P = .004). Conclusion: Romosozumab significantly increased BMD at the lumbar spine, total hip and femoral neck after 12 months of treatment. The response was more pronounced in patients without diabetes and those who were treatment-naïve, suggesting that metabolic status and previous antiresorptive therapy may influence treatment effectiveness. Prospective studies are warranted to evaluate long-term fracture outcomes and the durability of these effects.
Background: Dyslipidemia is a condition where lipid metabolism is altered, and its mechanism is closely related to non-alcoholic fatty liver disease. The alteration of lipid metabolism during non-alcoholic fatty liver disease results in disrupted uptake, oxidation, and export. Assessing dyslipidemia among non-alcoholic fatty liver disease using these lipid panel is affordable, widely available, and compatible with existing laboratory infrastructure which enables for identifying individuals at increased risk of its complications, guiding therapeutic interventions, and supporting metabolic risk management. Objective: The study aimed to assess Dyslipidemia and its associated factors among non-alcoholic fatty liver disease-diagnosed type 2 diabetes mellitus patients in Adama Hospital Medical College, 2024. Methods: An institution-based cross-sectional study design was used, and the study units were selected using a systematic random sampling technique. Sociodemographic, Behavioral, and Clinical data were collected using a structured questionnaire. Anthropometric measurements were taken by experienced nurses. Fasting venous blood was collected to test the lipid profiles and fasting blood glucose of study participants using Siemens Healthineers dimension EXL 200 chemistry analyzer. Data were assessed using STATA version 17 for correlation analysis among lipid parameters and the predictors, and P < .05 was considered statistically significant. Binary logistic regression was performed to show the statistically significant association among dyslipidemia and associated factors, and P < .05 was also considered statistically significant. Results: The overall proportion of dyslipidemia was found to be 199 (85.04%). High TG 128 (54.7%) and low HDL-C 121 (51.71%) accounts for the major abnormal lipid parameters. BMI, blood pressure, and non-alcoholic fatty liver disease showed a weak positive statistical correlation with increased LDL-C, TG, and TC and a weak negative statistical correlation with HDL-C. The odds of lack of regular exercise and non-alcoholic fatty liver disease were higher for developing dyslipidemia. Conclusions: The overall prevalence of dyslipidemia was found to be high among non-alcoholic fatty liver disease-diagnosed type 2 diabetes mellitus patients. Hypertriglyceridemia was found to be highly prevalent, followed by low HDL-C, and high LDL-C.
Background: To investigate the association between melatonin levels and bone mineral density (BMD) in postmenopausal women with type 2 diabetes mellitus (T2DM). Methods: One hundred and ninety postmenopausal women who visited the clinic between September 2023 and September 2024 were selected and divided into 4 groups according to their disease status: the normal group (n = 45); the abnormal bone mass group (n = 43); the T2DM group (n = 46); and the T2DM with abnormal bone mass group (n = 56). Relevant glycolipid metabolism biochemical indexes, bone metabolism markers and melatonin levels were detected and statistically analyzed. Results: Comparison of melatonin levels showed that melatonin levels were significantly lower in the abnormal bone mass group, the T2DM group, and the T2DM with abnormal bone mass group [100.00 (94.00, 110.00), 99.00 (91.75, 100.25), and 92.50 (84.75, 99.00)] than in the normal group [127.71 (116.23, 137.68)], and melatonin levels were the lowest in the T2DM with abnormal bone mass group ( P < .01). Melatonin levels were positively correlated with both lumbar spine L1 to L4 BMD and femoral neck BMD. T2DM differed in the role of melatonin in associating with BMD at different sites. For lumbar spine L1 to L4 BMD, the mediating effect of T2DM was not significant (percentage: −8.16%, 95% CI, −90.39 to 57.00), and for femoral neck BMD, T2DM played a significant mediating role, with its effect accounting for 33.95% (95% CI, 5.38-70.00) of the total effect. Receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) of the operating characteristics of subjects with melatonin levels diagnosing osteoporosis (OP) was 0.942 (95% CI, 0.902-0.982). The optimal cut-off value was 124.29 pg/mL when the Jordon index was 0.571, corresponding to a sensitivity and specificity of 57.8% and 99.3%, respectively. Multiple linear regression analysis showed that a decreased melatonin level was a risk factor for decreased BMD. Conclusion: Lower serum melatonin levels in postmenopausal women with T2DM are an independent risk factor for decreased BMD, and T2DM partially mediates the protective effect of melatonin on femoral neck BMD. Serum melatonin levels have a specific diagnostic value for abnormal bone mass in postmenopausal women with T2DM.
With the introduction of sodium-glucose cotransporter inhibitors, the incidence and awareness of euglycemic DKA have been increasing. This condition is a distinct subset of DKA without marked hyperglycemia. It can arise in various clinical settings, present with non-specific symptoms, and is thus prone to underdiagnosis. A set of circumstances (SGLT2i users during major stress, pregnancy with diabetes), clinical findings (non-specific GI symptoms, lassitude), and biochemical changes (ketonemia and metabolic acidosis) are consistent findings in the majority of cases of euglycemic DKA. Awareness that diabetic ketoacidosis can occur with normoglycemia, and leveraging the use of blood ketone tests, including meter kits, will significantly improve the diagnosis of euglycemic DKA.
Background: Graves’ disease (GD) ranks as a primary cause of hyperthyroidism across all age demographics. The clinical presentation, treatment approaches, and overall therapeutic objectives can differ among various age groups. This study aimed to describe the clinical, laboratory, and radiological features, as well as the outcomes of the management of GD within the Saudi pediatric population. Methods: A cross-sectional, multicenter study across 2 tertiary care centers in Saudi Arabia (2010-2021). Clinical, biochemical, and imaging data were collected for children diagnosed with hyperthyroidism under the age of 18, utilizing an electronic medical records system. Data were analyzed using the Statistical Package for the Social Sciences (SPSS) version 21. Results: We enrolled 93 patients with hyperthyroidism (Mean age at diagnosis = 11.5 years; females = 68, 73.1%). Notably, 40/93 patients (43%) had a significant family history. The primary etiologies were GD (N = 60, 64.5%) and hashitoxicosis (N = 10, 10.8%). The commonest presentations were goiter (57%) and tachycardia (55%). GD was predominantly associated with exophthalmos, lid lag, sweating, tremors, and weight loss (Odds Ratios = 3.71, 3.8, 2.77, 2.34, and 2.28, respectively). An increase in thyroid radioactive iodine uptake was observed in 29/93 patients (48.3%; P -value = .029), in contrast to non-sensitive thyroid ultrasound results ( P -value = .228). Thyroid Stimulating Immunoglobulin (TSI; N = 9.1, P -value = .000), Anti-thyroglobulin (TG; N = 537.5, P -value = .018), and Anti-thyroid peroxidase (TPO; N = 366.5, P -value = .017) were significant alongside FT4 and FT3 ( P -value = .000) in diagnosing GD. Most patients were treated exclusively with methimazole (MMT), showing good compliance (N = 44, 73%) and minimal adverse effects (N = 56, 93.3%). Radioactive iodine (RAI) ablation was performed in 14 patients (23.3%), and thyroidectomy in 5 patients (8.3%). Conclusion: In our cohort, GD emerged as a leading cause of hyperthyroidism among children and adolescents. Pediatric endocrinologists in Saudi Arabia tend to underutilize RAI and prefer alternative treatment methods.
Background:Moderate-to-severe thyroid eye disease (TED) is a potentially vision-threatening inflammatory condition that requires timely, evidence-based medical management. Although intravenous glucocorticoids remain the mainstay of therapy, several biologic and immunosuppressive agents have emerged as potential alternatives, particularly in steroid-refractory disease. Objectives:To evaluate and compare the efficacy, safety, and therapeutic positioning of medical treatments for active moderate-to-severe thyroid eye disease. Data Sources and Methods:A comprehensive search of PubMed, Embase, and the Cochrane Library was conducted through February 2025. Eligible studies included randomized controlled trials, meta-analyses, systematic reviews, observational cohorts, and selected case series evaluating pharmacological interventions for moderate-to-severe TED. Outcomes of interest were proptosis reduction, Clinical Activity Score (CAS) improvement, diplopia response, and safety/tolerability. A semi-quantitative synthesis approach was used to integrate evidence across heterogeneous study designs. Results:Fifty-eight studies met the inclusion criteria. Intravenous glucocorticoids (IVGCs) demonstrated the most consistent efficacy in controlling inflammatory activity, with modest effects on proptosis and favorable tolerability at cumulative doses below 8 g. Among biologic therapies, teprotumumab showed the greatest magnitude of benefit across all efficacy domains but was limited by safety considerations and access constraints. Rituximab and tocilizumab demonstrated moderate efficacy, particularly in glucocorticoid-resistant cases. Mycophenolate mofetil emerged as the most reliable non-biologic immunosuppressive option. Oral glucocorticoids and several adjunctive therapies showed limited or inconsistent benefit. Conclusion:This systematic review provides an integrated framework to support therapeutic decision-making in moderate-to-severe TED. Intravenous glucocorticoids remain the most consistently supported first-line therapy, while IGF-1R-targeted biologic therapy offers the most comprehensive efficacy across key clinical domains in selected patients. Registration:Not registered.
Cardiovascular diseases are the leading cause of global mortality, accounting for roughly one-third of all deaths. Dyslipidemia is a key risk factor for atherosclerotic cardiovascular disease (ASCVD) and often coexists with diabetes, which exacerbates ASCVD risk. Despite the comprehensive management of dyslipidemia in patients with diabetes through pharmacological and non-pharmacological approaches, many individuals struggle to meet lipid targets through lifestyle changes alone. Therefore, pharmacological interventions are essential. Pharmacotherapy options for dyslipidemia in patients with diabetes, including those currently under development, have gained attention, particularly regarding their impact on cardiovascular outcomes. In this narrative review, we explore the data on cardiovascular outcomes related to established and emerging pharmacotherapy in the management of dyslipidemia in diabetes, such as statins, ezetimibe, bempedoic acid, PCSK9 inhibitors, icosapent ethyl, inclisiran, other lipid-lowering agents (fibrates, bile acid sequestrants, niacin), and novel medications such as antisense nucleotides and cholesterol ester transfer protein inhibitors. We aim to provide a summary that will help navigate the extensive evidence base on cardiovascular outcomes trials of these agents. We found that statins, particularly atorvastatin, showed the strongest and most consistent evidence on cardiovascular outcomes in patients with diabetes, with high-intensity statin therapy associated with significant reductions in major adverse cardiovascular events (MACE). Therefore, clinicians should prioritize statin therapy as the first-line pharmacotherapy for managing dyslipidemia in patients with diabetes to optimize cardiovascular outcomes. Studies also showed that the duration of statin therapy is the strongest predictor of MACE, followed by the achieved LDL cholesterol level and statin intensity. Additional lipid-lowering agents, such as ezetimibe or PCSK9 inhibitors, should be considered for patients who do not achieve target LDL cholesterol levels or for those who are statin-intolerant.
Impaired pancreatic β-cell function is a key feature in the pathophysiology of both type 1 and long-standing type 2 diabetes. C-peptide, produced in 1:1 ratio along with insulin, is secreted at a relatively steady rate over long duration, making it an effective biomarker for endogenous insulin secretion. Given the heterogeneity and complex pathophysiology of diabetes, C-peptide estimation plays an important role in the accurate classification of diabetes and in guiding treatment decisions, particularly for patients needing insulin therapy. In autoimmune diabetes, especially adult-onset forms, C-peptide has gained importance as a biomarker. However, its greatest utility is often observed 3 to 5 years post-diagnosis, when detectable C-peptide levels may help differentiate between MODY (Maturity-onset Diabetes of the Young) and type 2 diabetes. The clinical applications of C-peptide extend beyond diagnosis, including risk stratification for diabetes-related vascular complications, determining pharmacotherapy choices, evaluating hypoglycemia, and even in the context of bariatric surgery. Despite its usefulness, the role of C-peptide in type 2 diabetes remains limited, primarily due to insulin resistance, which may elevate C-peptide levels. Estimating C-peptide is a cost-effective and reliable method, but there is still considerable variation in its application. Factors such as sample collection, timing in relation to meals, and the lack of standardization in assay techniques raise issues regarding the consistency and repeatability of results among various laboratories. This review aims to explore the current evidence surrounding C-peptide estimation in diabetes care, as well as the limitations and uncertainties that continue to challenge its clinical application.
