Obesity in Prediabetic Patients: Management of Metabolic Complications and Strategies for Prevention of Overt Diabetes.

Obesity and prediabetes affect a substantial part of the general population, but are largely underdiagnosed, underestimated, and undertreated. Prediabetes differs from diabetes only in the degree of hyperglycaemia consequent to the progressive decline in residual beta-cell function. Both prediabetes and diabetes occur as a consequence of insulin resistance that starts several years before the clinical onset of overt diabetes. Macrovascular complications in patients with diabetes are mainly caused by insulin resistance. This is why in prediabetes, the overall cardiovascular risk is, by all means, similar to that in patients with diabetes. It is important, therefore, to identify prediabetes and treat patients not only to prevent or delay the onset of diabetes, but to reduce the cardiovascular risk associated with prediabetes. This review provides an overview of the pathophysiology of prediabetes in patients with obesity and the progression toward overt diabetes. We have reviewed nutritional and pharmacological approaches to the management of obesity and reduced glucose tolerance, and the treatment of the major comorbidities in these patients, including hypertension, dyslipidaemia, and Metabolic dysfunction-associated Steatotic Liver Disease (MASLD), has also been reviewed. In patients with obesity and prediabetes, the nutritional approach is similar to that adopted for patients with obesity and diabetes; treatments of dyslipidaemia and hypertension also have the same targets compared to patients with diabetes. MASLD is a critical issue in these patients; in the prediabetic state, MASLD rarely progresses into fibrosis. This highlights the importance of the early recognition of this pathological condition before patients become diabetic when the risk of fibrosis is much higher. It is necessary to raise awareness of the clinical relevance of this pathological condition in order to prompt early intervention before complications occur. The single most important therapeutic goal is weight loss, which must be early and persistent.

Diabetes as a risk factor for pneumococcal disease and severe related outcomes and efficacy/effectiveness of vaccination in diabetic population. Results from meta-analysis of observational studies.

AIMS: To collect all available evidence on the effect of diabetes mellitus (DM) as a risk factor for pneumococcal disease incidence and related complications, and on the efficacy/effectiveness of vaccines in patients with DM. METHODS: Two distinct systematic searches on MEDLINE, Cochrane, ClinicalTrials.gov and EMBASE databases were performed, one for each meta-analysis, collecting all observational (cohort and case-control) studies and randomized clinical trials performed on humans up to June 1st, 2023. RESULTS: We retrieved 36 observational studies comparing risk for pneumococcal disease and related complications in people with or without DM, and 11 studies (1 randomized clinical trial and 10 observational studies) assessing conjugated and polysaccaridic vaccines efficacy/effectiveness on preventing such outcomes. People with DM were at higher risk for Invasive Pneumococcal Disease (unadjusted OR 2.42 [2.00; 2.92]); Case-Fatality Rate (unadjusted OR 1.61 [1.25; 2.07], Pneumococcal pneumonia (unadjusted OR 2.98 [2.76; 3.22), and Intensive care unit admission for pneumococcal disease (unadjusted OR 2.09 [1.20; 3.66]). In diabetic individuals vaccinated with conjugated vaccine, incidence of pneumonia specific for vaccine type in a clinical trial (OR 0.237 [0.008; 0.704]), and hospitalization for overall pneumonia during the year following the polysaccharide vaccination in observational studies (unadjusted OR 0.63 [0.45-0.89]) were significantly lower in comparison with unvaccinated DM subjects, with no significant differences for other outcomes. CONCLUSIONS: People with diabetes mellitus are at higher risk for less favourable course of pneumococcal disease and should be therefore targeted in vaccination campaigns; more evidence needs to be collected on vaccination outcomes in people with diabetes.

Early Detection of Microvascular Changes in Patients with Diabetes Mellitus without and with Diabetic Retinopathy: Comparison between Different Swept-Source OCT-A Instruments.

Optical coherence tomography angiography (OCT-A) has recently improved the ability to detect subclinical and early clinically visible microvascular changes occurring in patients with diabetes mellitus (DM). The aim of the present study is to evaluate and compare early quantitative changes of macular perfusion parameters in patients with DM without DR and with mild nonproliferative DR (NPDR) evaluated by two different swept-source (SS) OCT-A instruments using two scan protocols (3 × 3 mm and 6 × 6 mm). One hundred eleven subjects/eyes were prospectively evaluated: 18 healthy controls (control group), 73 eyes with DM but no DR (no-DR group), and 20 eyes with mild NPDR (DR group). All quantitative analyses were performed using ImageJ and included vessel and perfusion density, area and circularity index of the FAZ, and vascular complexity parameters. The agreement between methods was assessed according to the method of Bland-Altman. A significant decrease in the majority of the considered parameters was found in the DR group versus the controls with both instruments. The results of Bland-Altman analysis showed the presence of a systemic bias between the two instruments with PLEX Elite providing higher values for the majority of the tested parameters when considering 6 × 6 mm angiocubes and a less definite difference in 3 × 3 mm angiocubes. In conclusion, this study documents early microvascular changes occurring in the macular region of patients at initial stages of DR, confirmed with both SS OCT-A instruments. The fact that early microvascular alterations could not be detected with one instrument does not necessarily mean that these alterations are not actually present, but this could be an intrinsic limitation of the device itself. Further, larger longitudinal studies are needed to better understand microvascular damage at very early stages of diabetic retinal disease and to define the strengths and weaknesses of different OCT-A devices.

Baseline glucose homeostasis predicts the new onset of diabetes during statin therapy: A retrospective study in real life.

OBJECTIVE: We evaluated the risk of altered glucose levels and new-onset diabetes (NOD) associated with statins according to glucose levels at baseline in a population treated for dyslipidemia on primary prevention for >5 years. DESIGN: The retrospective study included 308 subjects (265 on statins and 43 controls on diet) with a follow-up of 5-15 years. The cohort was classified according to glucose tolerance at both baseline and follow-up. RESULTS: The cumulative incidence of NOD was 13.6% (9.3% in controls and 13.5% in treated patients). NOD was diagnosed after 3.4±1.8 years. In the group with normal glucose levels at baseline, a family history of diabetes (OR: 3.4, 95% CI 1.3-8.9), BMI >30 kg/m2 (OR: 8.5, 95% CI 2.0-35.8), treatment with thiazide (OR: 21.9, 95% CI 1.2-384.2) and no alcohol consumption (OR: 0.3, 95% CI 0.1-0.8) reduced the risk of developing altered glucose levels or NOD. No effects of statins were seen. In the group with altered glucose levels at baseline, hypertension (OR: 5.0, 95% CI 1.0-25.3) and hypertriglyceridemia (OR: 3.5, 95% CI 1.0-11.8) increased the risk of remaining with altered glucose levels or developing NOD. Treatment with statins (OR: 7.5, 95% CI 1.5-37.4), in particular atorvastatin, was associated with an increased risk. In the whole population, statin therapy (OR: 4.0, 95% CI 1.1-14.1, p<0.020), and in particular simvastatin and atorvastatin, was associated with increased risk of altered glucose levels or NOD. Patients who developed or maintained altered glucose levels or NOD had a poor metabolic phenotype at baseline. CONCLUSIONS: Statins were associated with an increased risk of NOD or altered glucose levels, mainly in subjects with altered glucose levels before the beginning of therapy. Poor metabolic phenotype and unhealthy behaviors or family history of diabetes contributed to that risk.

Does statin therapy reduce plasma VEGF levels in humans? A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The effect of statins on plasma concentrations of vascular endothelial growth factor (VEGF), the main angiogenic growth factor with pro-inflammatory and atherogenic properties, is controversial. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to obtain a conclusive result in humans. METHODS: PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases were searched to identify RCTs investigating the impact of statins on plasma VEGF concentrations. A random-effects model and the generic inverse variance method were used for quantitative data synthesis. Meta-regression, sensitivity analysis and publication bias assessments were performed using standard methods. RESULTS: Eight RCTs examining the effects of statins on plasma VEGF concentrations were included. Meta-analysis suggested a significant reduction of plasma VEGF levels following statin therapy (weighed mean difference: -19.88 pg/mL, 95% CI: -35.87, -3.89, p=0.015). VEGF reductions were observed in the subsets of trials with treatment durations ≥4 weeks (-19.54, -37.78, -1.30, p=0.036), LDL-C reductions ≥50 mg/dL (-28.59, -43.68, -13.50, p<0.001), lipophilic statins (-22.31, -40.65, -3.98, p=0.017), and diseased populations (-21.08, -39.97, -2.18, p=0.029), but not in the opposite subsets. Meta-regression also suggested a significant association between changes in plasma VEGF levels and LDL-C changes, treatment duration, but not molar dose of statins. CONCLUSIONS: These results suggest a significant reduction in plasma VEGF concentrations following statin therapy. This effect depends on duration of treatment, LDL-lowering activity, lipophilicity of statins, and health status of studied individuals. Further RCTs are needed to explore if the VEGF reduction is implicated in the statin benefits on cardiovascular outcomes.

One-year treatment with liraglutide improved renal function in patients with type 2 diabetes: a pilot prospective study.

Unlike GLP-1, liraglutide is not cleared by the glomerulus and its pharmacokinetic is not altered in patients with mild renal impairment. The aim of our study was to analyze the effects of liraglutide on renal function in patients with type 2 diabetes. A twelve-month longitudinal prospective post-marketing study was performed. According to eGFR (estimated glomerular filtration rate) calculated with CKD-EPI equation, 84 consecutive patients were divided in Group A (eGFR > 90 ml/min) and Group B (eGFR < 90 ml/min). BMI, glucose, HbA1c, serum creatinine, microalbuminuria, and eGFR were evaluated at baseline and after 12 months of treatment. A reduction in fasting plasma glucose (p < 0.01), HbA1c (p < 0.003), BMI (p < 0.01), and systolic (p < 0.01) and diastolic blood pressure (p < 0.006) was recorded irrespective of eGFR category. Concerning renal function, creatinine levels had a trend to decrease in both groups. eGFR did not change in Group A, while it increased in Group B (p < 0.05) independently from the concomitant changes of other parameters. Moreover, seven out of 41 patients of Group B had increased eGFR levels which reached the normal values (>90 ml/min). At baseline, five patients had pathological microalbuminuria, but at 12 months three of them returned to normal albuminuria (p < 0.006). Total microalbuminuria levels improved in both groups (p < 0.02). According to preliminary data in animals, our study shows that liraglutide is effective in preserving eGFR in diabetic patients, increasing it in those with reduced renal function. This was associated with a decrease of frequency of patients positive to microalbuminuria. Further studies are needed to confirm these data.