Adherence to GLP1-RA and SGLT2-I affects clinical outcomes and costs in patients with type 2 diabetes.

AIMS: To evaluate the impact of adherence to glucagon like peptide-1 receptor agonists (GLP1-RA) and sodium-glucose transporter two inhibitors (SGLT2-I) on clinical outcomes and costs in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: The 121,115 residents of the Lombardy Region (Italy) aged ≥40 years newly treated with metformin during 2007-2015 were followed to identify those who started therapy with GLP1-RA or SGLT2-I. Adherence to drug therapy over the first year was defined as the proportion of days covered >80%. Within each drug class, for each adherent patient, one non-adherent patient was matched for age, sex, duration, adherence to metformin treatment and propensity score. The primary clinical outcome was a composite of insulin initiation, hospitalisation for micro- and macrovascular complications and all-cause mortality after the first year of drug treatment. Costs were evaluated based on reimbursements from the national healthcare system. RESULTS: After matching, 1182 pairs of adherent and non-adherent GLP1-RA users and 1126 pairs of adherent and non-adherent SGLT2-I users were included. In both groups, adherent patients experienced a significantly lower incidence of the primary outcome (HR: 0.85, 95% CI 0.72-0.98 for GLP1-RA and HR: 0.69, 95% CI 0.55-0.87 for SGLT2-I). A significant reduction in hospitalizations was found for adherent patients in the GLP1-RA group but not for the SGLT2-I group. Results were consistent when analyses were stratified by age and sex. While higher drug-related costs in the adherent group were counterbalanced by decreased hospitalisation costs in SGLT2-I treated patients, this was not the case for GLP1-RA. CONCLUSIONS: Higher adherence to drug treatment with GLP1-RA and SGLT2-I during the first year of the drug intake is associated with a lower incidence of adverse clinical outcomes in a real-world setting.

Impact of MASLD and MetALD on clinical outcomes: A meta-analysis of preliminary evidence.

A recent Delphi consensus proposed a new definition for metabolic dysfunction associated steatotic liver disease (MASLD) and introduced a disease entity called MetALD, a condition in which steatotic liver disease (SLD), metabolic dysfunction and moderate alcohol intake coexist. Given the limited available data on the prognostic implications of these disease entities, we performed a systematic review and meta-analysis of available cohort studies to evaluate the association of MASLD and MetALD with hard clinical outcomes. We included 5 studies for a total of 9 824 047 participants. Compared with participants without SLD, increased rates of all-cause mortality and incident cardiovascular disease were present for both MASLD and MetALD. Moreover, MetALD was also associated with significantly higher risks of cancer-related mortality (n = 2 studies, random-effects HR 2.10, 95% CI 1.35-3.28) and cardiovascular mortality (n = 3 studies, random-effects HR 1.17, 95% CI 1.12-1.22). Although preliminary, available evidence indicates a more unfavourable prognosis for patients with MetALD compared with those with MASLD.

Liver fibrosis, NT-ProBNP and mortality in patients with MASLD: A population-based cohort study.

BACKGROUND & AIM: Liver fibrosis is the strongest predictor of liver-related mortality in many chronic liver diseases. NT-ProBNP is independently associated with cardiovascular mortality in general population settings. Here, we evaluate the relative contribution of non-invasively identified liver fibrosis and NT-ProBNP on all-cause and cardiovascular mortality in patients with metabolic (dysfunction)-associated steatotic liver disease (MASLD). METHODS AND RESULTS: Serum NT-ProBNP levels were measured in 4229 patients with MASLD from the general population without a known history of heart failure that participated in the 1999-2004 cycles of the National Health and Nutrition Examination Survey. Presence of liver fibrosis was estimated using the Fibrosis-4 index (FIB-4). We applied Cox proportional hazard models adjusted for cardiovascular risk factors to evaluate the association between NT-ProBNP and FIB-4 levels and all-cause and cardiovascular mortality through December 2019. Mortality was lower for participants with normal levels of both biomarkers, intermediate if a single biomarker was elevated and highest when both were above the chosen threshold. In the multivariable-adjusted models, both elevated FIB-4 (≥2.67) and elevated NT-ProBNP levels (≥125 pg/ml) were independently associated with higher risks of all-cause mortality (HR 2.2, 95 % CI 1.5-3.2 and HR 1.6, 95 % CI 1.4-2.0, respectively) and cardiovascular mortality (HR 2.1, 95 % CI 1.2-3.7 and HR 2.1, 95 % CI 1.5-2.9, respectively). The associations remained consistent in subgroup analyses based on sex, obesity and age. CONCLUSIONS: Both FIB-4 and NT-ProBNP are independently associated with higher mortality in patients with MASLD. Their combined use might prove useful to risk-stratify patients in clinical practice.

Adherence to antidiabetic drug therapy and reduction of fatal events in elderly frail patients.

BACKGROUND: To evaluate the protective effect of oral antidiabetic drugs in a large cohort of elderly patients with type 2 diabetes differing for age, clinical status, and life expectancy, including patients with multiple comorbidities and short survival. METHODS: A nested case-control study was carried out by including the cohort of 188,983 patients from Lombardy (Italy), aged ≥ 65 years, who received ≥ 3 consecutive prescriptions of antidiabetic agents (mostly metformin and other older conventional agents) during 2012. Cases were the 49,201 patients who died for any cause during follow-up (up to 2018). A control was randomly selected for each case. Adherence to drug therapy was measured by considering the proportion of days of the follow-up covered by the drug prescriptions. Conditional logistic regression was used to model the risk of outcome associated with adherence to antidiabetic drugs. The analysis was stratified according to four categories of the clinical status (good, intermediate, poor, and very poor) differing for life expectancy. RESULTS: There was a steep increase in comorbidities and a marked reduction of the 6-year survival from the very good to the very poor (or frail) clinical category. Progressive increase in adherence to treatment was associated with a progressive decrease in the risk of all-cause mortality in all clinical categories and at all ages (65-74, 75-84 and ≥ 85 years) except for the frail patient subgroup aged ≥ 85 years. The mortality reduction from lowest to highest adherence level showed a tendency to be lower in frail patients compared to the other categories. Similar although less consistent results were obtained for cardiovascular mortality. CONCLUSIONS: In elderly diabetic patients, increased adherence to antidiabetic drugs is associated with a reduction in the risk of mortality regardless of the patients' clinical status and age, with the exception of very old patients (age ≥ 85 years) in the very poor or frail clinical category. However, in the frail patient category the benefit of treatment appears to be less than in patients in good clinical conditions.

Low 25 (OH) vitamin D levels are associated with increased prevalence of nonalcoholic fatty liver disease and significant liver fibrosis.

AIMS: Evidence on the role of 25-Hydroxyvitamin D (25(OH)D) in the occurrence and progression of nonalcoholic fatty liver disease (NAFLD) is conflicting and population-based data are scarce. Here, we assess the association between 25(OH)D levels, NAFLD and liver fibrosis in the general population. MATERIALS AND METHODS: This is an analysis of data from the 2017-2018 cycle of the National Health and Nutrition Examination Survey. We included adult participants with available data on vibration-controlled transient elastography (VCTE) and without viral hepatitis and significant alcohol consumption. Steatosis and fibrosis were diagnosed by the median values of controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), respectively. 25(OH)D was measured by high performance liquid chromatography-tandem mass spectrometry. RESULTS: A total of 3970 participants (1928 men and 2042 women) were included in the study. The prevalence of NAFLD (CAP ≥ 274 dB/m) and significant liver fibrosis (LSM ≥ 8 kPa) were 41.7% (95% CI 39.4-44.0) and 8.4% (95% CI 7.0-9.9), respectively, while 21.1% (95% CI 17.3-25.4) of participants had low 25(OH)D levels (<50 nmol/L). A multivariable logistic regression model adjusted for age, sex, race-ethnicity, body mass index, waist circumference, calendar period, diabetes, chronic kidney disease, and vitamin D supplementation showed that compared with participants with low 25(OH)D, those with optimal levels (≥75 nmol/L) had lower odds of both NAFLD (OR 0.73, 95% CI 0.55-0.98 p = 0.038) and significant liver fibrosis (OR 0.65, 95% CI 0.44-0.96, p = 0.033). CONCLUSIONS: An inverse relationship was found between 25(OH)D and NAFLD and fibrosis, suggesting a possible role of vitamin D in NAFLD occurrence and progression.

Trends in prevalence of probable fibrotic non-alcoholic steatohepatitis in the United States, 1999-2016.

Data are limited on the epidemiology of fibrotic non-alcoholic steatohepatitis (NASH). We applied the recently proposed Fibrotic NASH Index (FNI) to estimate trends in the prevalence of probable fibrotic NASH in the general United States population using data from the 1999-2016 cycles of the National Health and Nutrition Examination Survey. A total of 40 273 participants aged 20 years and older were included in the analysis. The prevalence of probable fibrotic NASH (FNI ≥0.33) in the overall population was 8.4% (95% CI 8.0-8.8), with higher values found in males and in Hispanic participants. It increased from 6.9% (95% CI 6.3-7.6) in 1999-2004 to 9.2% (95% CI 8.4-10.0) in 2011-2016. This positive trend was evident in both sexes and in participants with obesity and diabetes. Finally, it increased progressively with increasing age, body mass index and worse glucose tolerance. NASH prevalence is increasing in the general US population, synchronous with increasing rates of obesity and type 2 diabetes.

Liver stiffness is associated with all-cause mortality in patients with NAFLD: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Several studies reported an association between liver stiffness measurement (LSM) obtained through vibration-controlled transient elastography (VCTE) and all-cause mortality in patients with nonalcoholic fatty liver disease (NAFLD). The objective of this systematic review and meta-analysis was to summarize available evidence on the nature and magnitude of this association. METHODS: We systematically searched PubMed-MEDLINE and Scopus up to April 2023 for observational cohort studies in which LSM was measured with VCTE in patients with NAFLD or in general population settings, with a follow-up ≥1 year and with available data on all-cause mortality. Measures of association from individual studies were meta-analysed using random effects models. Of the 517 titles initially scrutinized, we included seven studies with data on 18 771 participants (47.1% male) and a mean follow-up of 3.6 years. We included effect estimates obtained in the models with the highest degree of adjustment for potential confounders available in each study. RESULTS: When analysed as a categorical variable based on specific LSM cut-offs, liver fibrosis was associated with an increased risk of all-cause death (HR 2.10, 95% CI 1.56-2.83; test for overall effect z = 4.919, p < 0.001). Results were consistent when LSM was considered as a continuous variable (HR for 1 kPa increase: 1.03, 95% CI 1.01-1.05; test for overall effect z = 3.341, p = 0.001). There was borderline significant heterogeneity among the studies (I2 = 50.2% and I2 = 66.7% in the two analyses, respectively). No significant publication bias was detected by funnel plot analysis and Egger's and Begg's tests. CONCLUSION: The present meta-analysis indicates that LSM, as a proxy of liver fibrosis, is independently and directly associated with a higher mortality risk in patients with NAFLD.

Exploring the landscape of steatotic liver disease in the general US population.

BACKGROUND AND OBJECTIVE: The aim of the present study is to explore the epidemiologic impact of the definition of steatotic liver disease (SLD) proposed by a multi-society (American Association for the Study of the Liver-the European Association for the Study of Liver Diseases-Asociación Latinoamericana para el Estudio del Hígado) Delphi consensus statement. METHODS: This is a cross-sectional study of US adults participating in the 2017-2020 cycles of the National Health and Nutrition Examination Survey who were evaluated by vibration-controlled transient elastography. Hepatic steatosis and fibrosis were diagnosed by the median value of controlled attenuation parameter and liver stiffness measurement using cut-offs of 274 dB/m and 8.0 kPa, respectively. Recently proposed criteria for metabolic dysfunction-associated steatotic liver disease (MASLD), MetALD (MASLD + significant alcohol consumption), MASLD-Viral hepatitis and cryptogenic SLD were applied. RESULTS: SLD was present in 42.1% (95% CI: 40.3-43.9) of the 3173 included participants. Among patients with SLD, 99.4% met the metabolic dysfunction definition. Moreover, 89.4%, 7.7%, 2.4%, 0.4% and 0.1% were defined as MASLD, MetALD, MASLD-Viral, alcoholic liver disease (ALD) (significant alcohol consumption without metabolic dysfunction) and cryptogenic, respectively. No patients without metabolic dysfunction had significant liver fibrosis, which was present in 15.2%, 9.5% and 19.5% of patients with MASLD, MetALD and MASLD-viral, respectively. Approximately, 90% of the overall adult US population could be diagnosed with metabolic dysfunction according to the consensus criteria. A high degree of concordance was found between MASLD and the previously proposed metabolic dysfunction-associated fatty liver disease definition. CONCLUSIONS: Metabolic dysfunction is present in almost all patients with SLD in the United States. The new change in diagnostic criteria did not significantly impact disease prevalence.

Cardioprotective Effects of Sodium Glucose Cotransporter 2 Inhibition in Angiotensin II-Dependent Hypertension Are Mediated by the Local Reduction of Sympathetic Activity and Inflammation.

The cardioprotective effects of sodium glucose cotrasponter 2 (SGLT2) inhibitors seem to be independent from the effects on glycemic control, through little-known mechanisms. In this study, we investigate whether the cardioprotective effects of empagliflozin, a SGLT2 inhibitor, may be associated with myocardial sympathetic activity and inflammatory cell infiltration in an experimental model of angiotensin II-dependent hypertension. Angiotensin II (Ang II), Ang II plus Empagliflozin, physiological saline, or physiological saline plus empagliflozin were administered to Sprague Dawley rats for two weeks. Blood pressure was measured by plethysmographic method. Myocardial hypertrophy and fibrosis were analysed by histomorphometry, and inflammatory cell infiltration and tyrosine hydroxylase expression, implemented as a marker of sympathetic activity, were evaluated by immunohistochemistry. Ang II increased blood pressure, myocardial hypertrophy, fibrosis, inflammatory infiltrates and tyrosine hydroxylase expression, as compared to the control group. Empagliflozin administration prevented the development of myocardial hypertrophy, fibrosis, inflammatory infiltrates and tyrosine hydroxylase overexpression in Ang II-treated rats, without affecting blood glucose and the Ang II-dependent increase in blood pressure. These data demonstrate that the cardioprotective effects of SGLT2 inhibition in Ang II-dependent hypertension may result from the myocardial reduction of sympathetic activity and inflammation and are independent of the modulation of blood pressure and blood glucose levels.

NT-ProBNP and mortality across the spectrum of glucose tolerance in the general US population.

BACKGROUND: Even though hyperglycemia is a well-known cardiovascular risk factor, the absolute risk of cardiovascular events varies to a great extent within each glycemic category. The aim of this study is to evaluate whether N-terminal pro-B natriuretic peptide (NT-ProBNP) could help identify subjects at higher cardiovascular risk, independently of blood glucose levels. METHODS: Serum NT-ProBNP levels were measured in 5502 people aged 45-79 years without heart failure from the general population (3380 with normoglycemia, 1125 with pre-diabetes and 997 with diabetes) that participated in the 1999-2004 cycles of the National Health and Nutrition Examination Survey. We applied Cox and Fine Gray models adjusted for cardiovascular risk factors to evaluate the association between NT-ProBNP levels and all-cause and cardiovascular mortality through December 2015. RESULTS: After a median follow-up of 13 years, 1509 participants died, 330 of cardiovascular causes. In the multivariable-adjusted models, compared with participants with NT-ProBNP < 100 pg/ml, those with levels 100-300 pg/ml and ≥ 300 pg/ml had a higher incidence of both all-cause mortality (HR 1.61, 95% CI 1.12-2.32, p = 0.012 and HR 2.96, 95% CI 1.75-5.00, p < 0.001, respectively) and cardiovascular mortality (HR 1.57, 95% CI 1.17-2.10, p = 0.011 and HR 2.08, 95% CI 1.47-2.93, p < 0.001, respectively). The association was consistent in subgroup analyses based on glycemic status, obesity, age and sex. CONCLUSIONS: Elevated NT-ProBNP is independently associated with all-cause and cardiovascular mortality in the general population and could help identify patients at the highest risk. Further studies are needed to evaluate whether intensification of treatment based on biomarker data might lead to improvements in cardiovascular risk reduction.

Body-weight variability and risk of cardiovascular outcomes in patients with type 1 diabetes: a retrospective observational analysis of data from the DCCT/EDIC population.

BACKGROUND: Cardiovascular risk and body-weight management are both emerging challenges of type 1 diabetes care. We evaluated the association between intraindividual variability of body-weight and risk of cardiovascular events in people with type 1 diabetes. METHODS: We analyzed 1,398 participants from the DCCT/EDIC studies. Five indices of intraindividual variability of body-weight were calculated for each participant taking into account body-weight measures obtained during the DCCT follow-up (average 6 ± 2 years). The Average Successive Variability (ASV) index, the main variable of interest, was defined as the average absolute difference between successive body-weight measures. The primary outcome was a composite of major adverse cardiovascular events (MACE: nonfatal myocardial infarction or stroke, or cardiovascular death) occurring during the subsequent EDIC follow-up (20 ± 3 years). All-cause death was a secondary outcome. Risk of outcomes were assessed by Cox proportional hazards regression analyses, adjusted for traditional cardiovascular risks factors, including BMI. RESULTS: The cumulative incidence of MACE and all-cause death during follow-up were 5.6% (n = 79) and 6.8% (n = 95), respectively. The adjusted Hazard Ratio (HR) for MACE by every increase of 1 standard deviation (SD) of ASV was 1.34 (95% CI, 1.06-1.66), p = 0.01. For all-cause death, the adjusted HR for 1 SD increase of ASV was 1.25 (1.03-1.50), p = 0.03. Similar results were observed when considering the other indices of intraindividual variability of body-weight. CONCLUSIONS: High body-weight variability (body-weight cycling) is associated with increased risk of MACE and all-cause death in people with type 1 diabetes, independently of the BMI and traditional cardiovascular risk factors.

Glycated albumin is associated with all-cause and cardiovascular mortality among U.S. adults with and without diabetes: A retrospective cohort study.

BACKGROUND AND AIMS: Glycated albumin (GA) reflects short-term glycemic control, but few data are available on its association with hard clinical outcomes. The purpose of this study is to evaluate the association between GA levels and all-cause and cardiovascular mortality in people with and without a previous diagnosis of diabetes. METHODS AND RESULTS: Serum GA levels were measured in 12147 people from the general population (1319 with and 10828 without diabetes) that participated in the 1999-2004 cycles of the National Health and Nutrition Examination Survey (NHANES). We evaluated the association between GA and all-cause and cardiovascular mortality through December 2015 by linking NHANES data with data from the National Death Index. Associations were compared with those observed for hemoglobin A1c (HbA1c). After a median follow-up of 13 years, 2785 participants (619 with and 2166 without diabetes) died, 651 of cardiovascular causes. Multivariable-adjusted Cox proportional hazard models showed that higher baseline GA levels were significantly associated with a higher incidence of both outcomes in participants with (all-cause: HR 1.03, 95% CI 1.01-1.04; cardiovascular: HR 1.04, 95% CI 1.02-1.07) and without diabetes (all-cause: HR 1.05, 95% CI 1.03-1.08; cardiovascular: HR: 1.08, 95% CI 1.02-1.14); on the other hand, we found a trend for increased mortality with increasing HbA1c levels in patients with known diabetes, but not in participants without. CONCLUSIONS: For a novel measure of hyperglycemia to be considered useful, its association with hard, long term clinical outcomes is of great importance. We showed that GA is associated with mortality in the general population independently of a previous diagnosis of diabetes.

Prevalence of Liver Steatosis and Fibrosis Detected by Transient Elastography in Adolescents in the 2017-2018 National Health and Nutrition Examination Survey.

BACKGROUND & AIMS: Metabolic-associated fatty liver disease (MAFLD) is common among adolescents, but the prevalence of significant fibrosis in this age group is not known. We aimed to estimate the prevalence of MAFLD and significant (≥F2) fibrosis by transient elastography (TE) in adolescents in the United States. METHODS: We analyzed TE data from participants 12-18 years old included in the National Health and Nutrition Examination Survey 2017-2018 (data available from 867 adolescents). Steatosis was evaluated by the median controlled attenuation parameter (CAP) and fibrosis by median liver stiffness measurement. RESULTS: Two-hundred forty participants (24.16%; 95% CI, 21.07-27.24) had any degree of steatosis (CAP≥248 dBm), 123 participants (11.6%; 95% CI, 9.19-14.06) had S3 steatosis (CAP≥280 dBm), and 51 participants (4.4%; 95% CI, 2.51-6.33) had significant fibrosis (liver stiffness ≥7.4 kPa). Multivariate analyses revealed that body mass index (odds ratio [OR] per unit increase, 1.2; 95% CI, 1.2-1.4), sex (OR female vs male participants , 0.5; 95% CI, 0.4-0.7), ethnicity (OR, Hispanic vs non-Hispanic white, 4.5; 95% CI, 1.7-11.8), and hypertension (OR, 3.5; 95% CI, 1.3-9.9) were associated with S3 steatosis, whereas body mass index (OR, 1.1 per unit increase; 95% CI, 1.0-1.2) and ethnicity (OR, non-Hispanic black vs non-Hispanic white, 3.9; 95% CI, 1.2-13.2) were associated with significant fibrosis. High proportions of participants with fibrosis were in the normal weight category (35%) and had normal levels of alanine aminotransferase (78%). CONCLUSIONS: Prevalence of MAFLD and significant fibrosis are alarmingly high in adolescents in the National Health and Nutrition Examination Survey 2017-2018. Levels of alanine aminotransferase and blood biomarkers do not correctly identify adolescents with more advanced disease. Effective noninvasive strategies to differentiate simple steatosis from progressive forms are urgently needed.

Baseline TSH levels and short-term weight loss after different procedures of bariatric surgery.

BACKGROUND: Bariatric surgery is a valuable therapeutic option in the treatment of obesity but the outcomes show a large subject-to-subject variability yet to be explained. Thyroid function may represent an involved factor and we have only few controversial data about its influence. SUBJECTS/METHODS: We retrospectively assessed using a longitudinal approach the relation between baseline TSH levels and short-term (6 and 12 months) weight loss in 387 euthyroid patients who underwent laparoscopic gastric banding (LAGB; n = 187) or sleeve gastrectomy (SG; n = 200). RESULTS: After LAGB, patients with low-normal TSH levels (0.40-1.40 mUI/L) had higher percent total weight loss, ∆BMI and percent excess weight loss when compared to patients with normal (1.41-2.48 mUI/L) and high-normal (2.49-4.00 mUI/L) TSH (p < 0.05). Conversely, no association was detected after SG (p = 0.17). The multivariable regression analysis showed that also baseline BMI (6-12 months) and HOMA2-IR (only at 6 months) were independently associated with the outcomes. CONCLUSIONS: TSH levels may influence the short-term weight loss response after LAGB. The lack of association after SG suggests that the influence of baseline endocrine and metabolic factors may not be relevant for procedures with greater and more immediate calorie intake restriction.

Renal protection: a leading mechanism for cardiovascular benefit in patients treated with SGLT2 inhibitors.

Initially developed as glucose-lowering drugs, sodium-glucose co-transporter type 2 inhibitors (SGLT2i) have demonstrated to be effective agents for the risk reduction of cardiovascular (CV) events in patients with type 2 diabetes mellitus (T2DM). Subsequently, data has emerged showing a significant CV benefit in patients treated with SGLT2i regardless of diabetes status. Renal protection has been initially evaluated in CV randomized trials only as secondary endpoints; nonetheless, the positive results gained have rapidly led to the evaluation of nephroprotection as primary outcome in the CREDENCE trial. Different renal and vascular mechanisms can account for the CV and renal benefits enlightened in recent literature. As clinical guidelines rapidly evolve and the role of SGLT2i appears to become pivotal for CV, T2DM, and kidney disease management, in this review, we analyze the renal effects of SGLT2, the benefits derived from its inhibition, and how this may result in the multiple CV and renal benefits evidenced in recent clinical trials.

Hypercortisolism and altered glucose homeostasis in obese patients in the pre-bariatric surgery assessment.

AIMS: Hypothalamus-pituitary-adrenal (HPA) axis hyperactivity was suggested to be associated with the metabolic syndrome (MS), obesity and diabetes. The aim of this study was to test whether hypercortisolism was associated with altered glucose homeostasis and insulin resistance, hypertension and dyslipidemia in a homogeneous population of obese patients. MATERIALS/METHODS: In retrospective analysis of a set of data about obese patients attending the outpatient service of a single obesity centre between January 2013 and January 2020, 884 patients with BMI >30 kg/m2 were segregated in two subgroups: patients with urinary free cortisol (UFC) higher than normal (UFC+; n = 129) or within the normal range (UFC-; n = 755). RESULTS: The overall prevalence of UFC+ was 14.6% and double test positivity (morning cortisol >1.8 mcg/dL following overnight dexamethasone suppression test, ODST) was detected in 1.0% of patients. Prediabetes (OR 1.74; 95%CI 1.13-2.69; p = 0.012) and diabetes (OR 2.03; 95%CI 1.21-3.42; p = 0.008) were associated with higher risk of UFC+ when analysis was adjusted for confounding variables. Conversely, hypertension and dyslipidemia were not related to UFC+. Within the individuals with normal FPG and HbA1c, those with higher estimated insulin resistance (HOMA2-IR) maintained a higher risk of UFC+ (OR 2.84, 95%CI 1.06-7.63; p = 0.039) and this relationship was weakened only when the body fat percentage was included into the model. CONCLUSIONS: In obese patients, hypercortisolism was more frequent across the entire spectrum of altered glucose homeostasis including the very early stages; this relation could not be detected for the other criteria of the MS, as waist, hypertension and atherogenic dyslipidemia.

Metabolic Syndrome, and Not Obesity, Is Associated with Chronic Kidney Disease.

INTRODUCTION: Obese (OB) patients are at increased risk of chronic kidney disease, but it is still unclear whether this can be attributed to obesity per se or to the associated metabolic derangements. The aim of this study was to evaluate the relative impact of obesity and metabolic syndrome (MS) on kidney disease. METHODS: This is a cross-sectional study based on data obtained in the 2005-2016 cycles of the National Health and Nutrition Examination Survey. We included all adult participants with available data on body mass index, estimated glomerular filtration rate (eGFR), urine albumin to creatinine ratio (UACR), and each of the MS components. Primary outcomes were eGFR <60 mL/min, UACR ≥30 mg/g, or a combination of the two. RESULTS: The studied population comprised 12,335 participants. OB participants without MS (OB+ MS-) were younger and more commonly female. After adjustment for potential confounders, compared with OB- MS- participants, an increased prevalence of albuminuria and reduced eGFR were present in both OB- MS+ groups and the OB+ MS+ groups, but not in the OB+ MS- groups. When each of the MS components was evaluated separately, elevated blood pressure and low high-density lipoprotein cholesterol were associated with both UACR and reduced eGFR, while elevated blood glucose and triglycerides were only associated with UACR. Waist circumference was not associated with any of the renal outcomes. DISCUSSION/CONCLUSION: This large cross-sectional study suggests that MS and not obesity is associated with kidney damage and that the OB+ MS- phenotype does not seem to carry an increased risk of kidney disease.

Prevalence of NAFLD, MAFLD and associated advanced fibrosis in the contemporary United States population.

Data are limited on the epidemiological implications of the recent change in terminology from nonalcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated fatty liver disease (MAFLD). We therefore performed a cross-sectional study of adults recruited in the 2017-2018 National Health and Nutrition Examination Survey, a representative sample of the general US population. The prevalence of NAFLD and MAFLD based on controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) obtained through vibration-controlled transient elastography (VCTE) were 37.1% (95% CI 34.0-40.4) and 39.1% (95% CI 36.3-42.1), respectively, with higher rates among Hispanic individuals. Agreement between the two definitions was high (Cohen's κ 0.92). Patients with NAFLD and MAFLD also showed similar risk of advanced liver fibrosis (7.5% and 7.4% respectively). Our results suggest that the recent change in diagnostic criteria did not affect the prevalence of the condition in the general United States population.

Sodium-glucose transporter 2 inhibitors for renal and cardiovascular protection in US adults with type 2 diabetes: Impact of the 2020 KDIGO clinical practice guidelines.

BACKGROUND: Sodium glucose transporter 2 inhibitors (SGLT2-i) reduce renal and cardiovascular events in patients with type 2 diabetes (T2D) and their use is recommended by the 2020 KDIGO guidelines in patients with T2D and chronic kidney disease (CKD). The aim of this study is to estimate the proportion of patients with T2D and CKD in the US that should be treated with these agents for renal and cardiovascular protection. METHODS: We conducted a retrospective analysis of 2005-2018 National Health and Nutrition Examination Survey (NHANES) data. We focused on participants with a prior diagnosis of diabetes or that met diagnostic criteria for diabetes during the survey, with the exclusion of probable type 1 diabetic patients. Inclusion criteria for completed and ongoing renal and cardiovascular outcome trials in patients with CKD were applied. RESULTS: We estimated that 35.3% of patients with T2D in the US (projected to 8.96 million) should be treated with SGLT2-i according to the 2020 KDIGO guidelines. Moreover, 2.9-10.1% (projected to 0.75-2.55 million) met the inclusion criteria for dedicated kidney outcome trials, which were focused on a population of individuals with proteinuria. CONCLUSIONS: About a third of patients with T2D in the US should be treated with an SGLT2-i. While compelling evidence of renal protection is present for patients with proteinuria, all patients with CKD obtain a cardiovascular benefit with this class of drugs.

Cost-effectiveness of the adherence with recommendations for clinical monitoring of patients with diabetes.

BACKGROUND AND AIMS: To validate a set of indicators for monitoring the quality of care of patients with diabetes in 'real-life' practice through its relationship with measurable clinical outcomes and healthcare costs. METHODS AND RESULTS: A population-based cohort study was carried out by including the 20,635 patients, residents in the Lombardy Region (Italy), who in the year 2012 were newly taken-in-care for diabetes. Adherence with clinical recommendations (i.e., controls for glycated haemoglobin, lipid profile, urine albumin excretion and serum creatinine) was recorded during the first year after the patient was taken-in-care, and categorized according whether he/she complied with none or almost none (0 or 1), just some (2) or all or almost all (3 or 4) the recommendations, respectively denoted as poor, intermediate and high adherence. Short- and long-term complications of diabetes, and healthcare cost incurred by the National Health Service, were assessed during follow-up. Compared with patients with poor adherence, those with intermediate and high adherence respectively showed (i) a delay in outcome occurrence of 13 days (95% CI, -2 to 27) and 23 days (9-38), and (ii) a lower healthcare cost of 54 € and 77 €. In average, a gain of 18 Euros and 15 Euros for each day free from diabetic complication by increasing adherence respectively from poor to intermediate and from poor to high were observed. CONCLUSION: Close control of patients with diabetes through regular clinical examinations must be considered the cornerstone of national guidance, national audits, and quality improvement incentive schemes.