MAFLD and glomerular hyperfiltration in subjects with normoglycemia, prediabetes and type 2 diabetes: A cross-sectional population study.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD, 2020 diagnostic criteria) and glomerular hyperfiltration share common risk factors, including obesity, insulin resistance, impaired glucose tolerance, diabetes, dyslipidemia, and hypertension. AIMS: To assess the prevalence of MAFLD and its association with glomerular hyperfiltration and age-related worsening of kidney function in subjects with normoglycemia, prediabetes and type 2 diabetes mellitus (T2DM). METHODS: We analysed data recorded during occupational health visits of 125,070 Spanish civil servants aged 18-65 years with a de-indexed glomerular filtration rate (GFR) estimated with the chronic-kidney-disease-epidemiological (CKD-EPI) equation (estimated glomerular filtration rate [eGFR]) ≥60 mL/min. Subjects were categorised according to fasting plasma glucose levels <100 mg/dL (normoglycemia), ≥100 and ≤ 125 mg/dL (prediabetes), or ≥126 mg/dL and/or antidiabetic treatment (T2DM). The association between MAFLD and glomerular hyperfiltration, defined as a de-indexed eGFR above the age- and gender-specific 95th percentile, was assessed by multivariable logistic regression. RESULTS: In the whole study group, MAFLD prevalence averaged 19.3%. The prevalence progressively increased from 14.7% to 33.2% and to 48.9% in subjects with normoglycemia, prediabetes and T2DM, respectively (p < 0.001 for trend). Adjusted odds ratio (95% CI) for the association between MAFLD and hyperfiltration was 9.06 (8.53-9.62) in the study group considered as a whole, and 8.60 (8.03-9.21), 9.52 (8.11-11.18) and 8.31 (6.70-10.30) in subjects with normoglycemia, prediabetes and T2DM considered separately. In stratified analyses, MAFLD amplified age-dependent eGFR decline in all groups (p < 0.001). CONCLUSIONS: MAFLD prevalence increases across the glycaemic spectrum. MAFLD is significantly associated with hyperfiltration and amplifies the age-related eGFR decline.

Mechanisms and treatment of obesity-related hypertension-Part 1: Mechanisms.

The prevalence of obesity has tripled over the past five decades. Obesity, especially visceral obesity, is closely related to hypertension, increasing the risk of primary (essential) hypertension by 65%-75%. Hypertension is a major risk factor for cardiovascular disease, the leading cause of death worldwide, and its prevalence is rapidly increasing following the pandemic rise in obesity. Although the causal relationship between obesity and high blood pressure (BP) is well established, the detailed mechanisms for such association are still under research. For more than 30 years sympathetic nervous system (SNS) and kidney sodium reabsorption activation, secondary to insulin resistance and compensatory hyperinsulinemia, have been considered as primary mediators of elevated BP in obesity. However, experimental and clinical data show that severe insulin resistance and hyperinsulinemia can occur in the absence of elevated BP, challenging the causal relationship between insulin resistance and hyperinsulinemia as the key factor linking obesity to hypertension. The purpose of Part 1 of this review is to summarize the available data on recently emerging mechanisms believed to contribute to obesity-related hypertension through increased sodium reabsorption and volume expansion, such as: physical compression of the kidney by perirenal/intrarenal fat and overactivation of the systemic/renal SNS and the renin-angiotensin-aldosterone system. The role of hyperleptinemia, impaired chemoreceptor and baroreceptor reflexes, and increased perivascular fat is also discussed. Specifically targeting these mechanisms may pave the way for a new therapeutic intervention in the treatment of obesity-related hypertension in the context of 'precision medicine' principles, which will be discussed in Part 2.

Daytime hypoglycemic episodes during the use of an advanced hybrid closed loop system.

AIMS: The use of advanced hybrid closed loop systems is spreading due to the beneficial effects on glycometabolic control obtained in patients with type 1 diabetes. However, hypoglycemic episodes can be sometimes a matter of concern. We aim to compare the hypoglycemic risk of an advanced hybrid closed loop system and a predictive low glucose suspend sensor augmented pump. METHODS: In this retrospective three months observational study, we included 30 patients using Medtronic Minimed™ 780G advanced hybrid closed loop system and 30 patients using a Medtronic Minimed™ predictive low glucose suspend sensor augmented pump. RESULTS: The advanced hybrid closed loop system reduced the time spent above 180 mg/dL threshold and increased the time in range as compared to the predictive low glucose suspend. No severe hypoglycemia occurred in both groups and no differences were observed in the percentage of time spent below 70 mg/dl and 54 mg/dl glucose threshold. Nevertheless, more hypoglycemic episodes were recorded during daytime, but not in nighttime, with the use of the advanced hybrid closed loop system. CONCLUSIONS: Our results confirmed the general improvement of glycemic outcomes obtained with the advanced hybrid closed loop system; however more hypoglycemic episodes during daytime were evident.