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Background and Aim: Bone as an endocrine organ regulates metabolic processes independently of mineral metabolism through the production/release of proteins collectively named 'osteokines'. Relevant connections were reported between the insulin/glucose system, calcification of the atherosclerotic plaque, and several osteokines. We aimed to test the hypothesis that the osteokine network could be involved in beta‐cell function, insulin sensitivity, and vascular damage in a cohort of people with newly diagnosed type 2 diabetes (T2D). Subjects and Methods: In 794 drug‐naive, GADA‐negative, newly‐diagnosed T2D patients (mean ± SD age: 59 ± 9.8 years; BMI: 29.3 ± 5.3 kg/m2; HbA1c: 6.6 ± 1.3%) we assessed: plasma concentration of osteocalcin (OCN), osteopontin (OPN), RANKL, and its putative decoy receptor osteoprotegerin (OPG); insulin sensitivity (SI) by hyperinsulinemic euglycemic clamp; beta cell function (BCF), estimated by OGTT minimal modelling and expressed as derivative (DC) and proportional (PC) control. Echo‐doppler of carotid and lower limb arteries were also performed in 708 and 701 subjects, respectively. Results: OCN, RANKL and OPG were significantly associated with PC (p < 0.02); OCN was positively related to DC (p = 0.018). OPG was associated with lower IS (p < 0.001). Finally, the higher RANKL levels, the greater was the severity of atherosclerosis in common carotid artery (p < 0.001). Increased OPG and OPN concentrations were related to subclinical atherosclerosis in peripheral arteries of lower limbs (p = 0.023 and p = 0.047, respectively). Conclusion: These data suggest that, in patients with newly diagnosed T2D, the osteokine network crosstalks with the glucose/insulin system and may play a role in modulating the atherosclerotic process. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the relationship of genetic variability of adiponectin (ADIPOQ), leptin (LEP) and leptin receptor (LEPR) genes with glucose‐insulin system and markers of subclinical atherosclerosis (ATS) in patients with newly diagnosed type 2 diabetes. Materials and methods: In 794 subjects we performed: 1) euglycemic hyperinsulinemic clamp to assess insulin sensitivity; 2) mathematical modelling of a 5h‐OGTT to estimate β‐cell function; 3) resting ECG; 4) carotid artery and lower limb artery eco‐doppler sonography to identify ATS; 5) genotyping of tag‐SNPs within ADIPOQ, LEP and LEPR gene. Results: Regression analyses showed: 1) adiponectin levels were negatively associated with BMI, waist‐to‐hip ratio and triglycerides and positively with HDL and insulin sensitivity (p‐all<0.03); 2) leptin levels were positively associated with BMI, HDL‐cholesterol and plasma triglycerides and negatively with insulin sensitivity (p‐all<0.001). Two SNPs (rs1501299 and rs2241767) within ADIPOQ gene were associated with circulating levels of adiponectin. The ADIPOQ‐GAACA haplotype was associated with plasma adiponectin (p=0.034; β=‐0.24), ECG abnormalities (p=0.012; OR=2.76), carotid ATS (p=0.025; OR=2.00) and peripheral limb artery ATS (p=0.032; OR=1.90). The LEP‐CTA haplotype showed an association with ischemic ECG abnormalities (p=0.017; OR=2.24). Finally, LEPR‐GAACGG was associated with circulating leptin (p=0.005; β=‐0.31) and worst β‐cell function (p=0.023; β=‐15.10). Omnibus haplotype analysis showed that ADIPOQ haplotypes were associated with levels of adiponectin and common carotid artery ATS, LEP with peripheral limb artery ATS, whereas LEPR haplotypes influenced circulating levels of leptin. Conclusions: Results of this study reinforce knowledge on adipokines' role in regulating glucose metabolism; in particular highlighted the potential atherogenic role of leptin and the anti atherogenic role of adiponectin. [ABSTRACT FROM AUTHOR]

Aim: Transition from paediatric to adult care is a critical step in life of emerging adults with type 1 diabetes. We assessed, according to indicators established by panel of experts, clinical, socio‐demographic and psychosocial factors in young adults with type 1 diabetes throughout structured transition to investigate the associations, if any, with HbA1c value at time of transition. Methods: The "Verona Diabetes Transition Project" started in January 2009: a structured transition program, shared between paediatric and adult clinic, was organised with a multi‐disciplinary team. All young adults underwent a semi‐structured interview by a psychologist, before transition. Minimum age for transition was 18 years. Results: 222 (M/F = 113/109) young adults moved to adult care from January 2009 to March 2020. The mean time between the last paediatric visit and the first adult visit ranged from 13.6 ± 6.1 months at the beginning of the project to 3.6 ± 11.5 months over the following years. At first adult clinic attendance, women showed higher HbA1c values (70 ± 11 mmol/mol vs. 65 ± 7 mmol/mol or 8.57% ± 1.51% vs. 8.14% ± 0.98%, p = 0.01), higher frequency of disorders of eating behaviours (15.6% vs. 0%, p < 0.001) and poor diabetes acceptance (23.9% vs. 9.7%, p < 0.001) than men. Mediation analyses showed a significant mediating role of glucose control 2 years before transition in the relationship between poor diabetes acceptance and glucose control at transition. Conclusions: This study demonstrated a delay reduction in establishing care with an adult provider and suggested the potential role of low diabetes acceptance on glycemic control at transition. Further studies are needed to confirm and expand these data. [ABSTRACT FROM AUTHOR]

Recent randomized controlled trials (RCTs) tested the efficacy of sodium-glucose cotransporter-2 (SGLT-2) inhibitors to specifically treat nonalcoholic fatty liver disease (NAFLD). We systematically searched three electronic databases (up to 31 October 2020) for identifying placebo-controlled or head-to-head RCTs that used SGLT-2 inhibitors for treatment of NAFLD. No published RCTs with paired liver biopsy data were available for the meta-analysis. Primary outcome measures were changes in serum liver enzyme levels and liver fat content on imaging techniques. Overall, we included a total of twelve RCTs testing the efficacy of dapagliflozin (n = six RCTs), empagliflozin (n = three RCTs), ipragliflozin (n = two RCTs) or canagliflozin (n = one RCT) to specifically treat NAFLD for a median period of 24 weeks with aggregate data on 850 middle-aged overweight or obese individuals with NAFLD (90% with type 2 diabetes). Compared to placebo/reference therapy, treatment with SGLT-2 inhibitors significantly decreased serum alanine aminotransferase (weighted mean differences (WMD): −10.0 IU/L, 95%CI −12.2 to −7.79 IU/L; I2 = 10.5%) and gamma-glutamyltransferase levels (WMD: −14.49 IU/L, 95%CI −19.35 to −9.63 IU/L, I2 = 38.7%), as well as the absolute percentage of liver fat content on magnetic resonance-based techniques (WMD: −2.05%, 95%CI −2.61 to −1.48%; I2 = 0%). In conclusion, SGLT-2 inhibitors seem to be a promising treatment option for NAFLD. [ABSTRACT FROM AUTHOR]

Aims: According to the 2023 International Consensus, glucose metrics derived from two-week-long continuous glucose monitoring (CGM) can be extrapolated up to 90 days before. However, no studies have focused on adults with type 1 diabetes (T1D) on multiple daily injections (MDIs) and with second-generation intermittently scanned CGM (isCGM) sensors in a real-world setting., Methods: This real-world, retrospective study included 539 90-day isCGM data from 367 adults with T1D on MDI therapy. For each sensor metric, the coefficients of determination ( R 2 ) were computed for sampling periods from 2 to 12 weeks versus the whole 90-day interval. Correlations were considered strong for R 2 ≥0.88., Results: The two-week sampling period displayed strong correlations for time in range (TIR, 70-180 mg/dl; R 2 = 0.89) and above range (TAR, >180 mg/dl; R 2 = 0.88). The four-week sampling period showed additional strong correlations for time in tight range (TITR, 70-140 mg/dl; R 2 = 0.92), for the coefficient of variation (CV; R 2 = 0.88), and for the glycemia risk index (GRI; R 2 = 0.92). The six-week sampling period displayed an additional strong correlation for time below range (TBR, <70 mg/dl; R 2 = 0.90). After stratification by clinical variables, lower R 2 values were found for older age quartiles (>40 years), higher CV (>36%), lower sensor use (≤94%), and higher HbA1c (>7.5%)., Conclusion: In patients with T1D on MDI, two- to six-week intervals of isCGM use can provide clinically useful estimates of TIR, TAR, TITR, TBR, CV, and GRI, which can be extrapolated to longer (up to 90 days) time intervals. Longer intervals might be needed in case of older age, higher glucose variability, lower sensor use, and higher HbA1c., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.