More than 25% of the adult population worldwide and approximately 50–75% of patients with type 2 diabetes are diagnosed with non-alcoholic fatty liver disease. Insulin resistance is one of the most crucial factors underlying its pathogenesis and a significant determinant of its progression to non-alcoholic steatohepatitis. The complex pathophysiology of non-alcoholic fatty liver disease emphasizes the need for combination treatment strategies with drug classes that target different cellular pathways, since no single agent can control all the mechanisms contributing to its development and evolution. Pioglitazone, the main thiazolidinedione in clinical practice, is the only true insulin sensitizing antidiabetic drug in our therapeutic armamentarium for the treatment of patients with type 2 diabetes. Current international practice guidelines recommend PIO as a promising therapy for patients who experience NASH and type 2 diabetes. GLP-1 receptor agonists and SGLT2 inhibitors have shown salutary cardiometabolic and renal effects in patients with type 2 diabetes, as well as beneficial liver activities in those with non-alcoholic fatty liver disease. This review discusses the pathophysiological background for the use of these three drug categories in patients with type 2 diabetes and non-alcoholic fatty liver disease. It also explores thoroughly the combinations of pioglitazone with either GLP-1 receptor agonists or SGLT2 inhibitors, as well as their future role in this setting.

Maternally inherited diabetes and deafness (MIDD) syndrome refers to a rarely diagnosed disorder caused by pathogenic variants in mtDNA. It was first identified in 1992 and, to date, is considered underdiagnosed because of misclassification to type 1 or type 2 diabetes mellitus. MIDD reflects a multisystem metabolic syndrome commonly resulting in insulin-requiring diabetes and sensorineural deafness but can also lead to a broad range of other manifestations. The spectrum of pathology differs among individuals, likely because of varied degrees of heteroplasmy associated with mtDNA. Heteroplasmy also creates diagnostic difficulties, with a high index of suspicion required to diagnose MIDD in some cases. Here, we review a patient with MIDD who presented with an atypical clinical diabetes picture, additionally documenting his pedigree. To our knowledge, this is the first Cypriot reported with MIDD.

Epstein-Barr virus (EBV) is a rare but well-known trigger for acute myositis. Diagnosis is primarily based on the clinical presentation and an accounting laboratory profile. Patients with mitochondrial dysfunction are potentially at a higher risk of myopathic exacerbations upon exposure to acute insults. This is due to the high energy requirements of myofibers and their reliance on sufficient mitochondrial performance. Hence, any mitochondrial insult can compromise the function of myofibers. This has implications on the management of people with pre-existing mitochondrial dysfunction, with scope for preventative measures and a lower threshold for diagnosis of myopathies. Usually, management is limited to conservative measures. Medications which predispose to muscle injury need to be withheld during the acute episode and their long-term need reviewed based on a risk-benefit analysis. Here, we present a case of acute EBV-induced myositis on a background of maternally inherited diabetes and deafness and chronic statin intake.

Advanced hybrid closed loop system (MiniMed 780G) achieving significant improvement of

Alzheimer’s disease (AD) and metabolic syndrome often occur together, sharing characteristics such as insulin resistance, dyslipidemia, and chronic inflammation. Metabolic dysfunction frequently precedes cognitive decline, indicating that early intervention might alter the disease’s progression. We investigated whether the GLP-1 receptor agonist semaglutide (SMGL) influences metabolic impairment and AD pathology in an AD mouse model. Male and female 5xFAD and wild-type (WT) mice on regular (RD) or high-fat diets (HFD) were administered SMGL for 13 weeks. SMGL-treated groups exhibited significant, context-dependent effects. In metabolically challenged 5xFAD HFD mice, treatment led to reduced body weight, improved glucose tolerance, normalized cholesterol levels, and a restored balance of adiponectin and leptin. These improvements were associated with reduced Aβ40 and Aβ42 levels, restored GLP-1 receptor expression, increased synaptophysin and βIII-tubulin levels, and enhanced spatial memory. SMGL also decreased Iba1 and CD68 immunoreactivity in the hippocampus and cortex, reduced macrophage infiltration, and lowered CD36 expression in visceral adipose tissue (VAT), indicating coordinated anti-inflammatory effects. WT RD mice showed minimal metabolic responses and a modest decline in Y-maze performance, suggesting that excessive GLP-1 receptor activation may disrupt neuronal homeostasis when metabolic status is normal. SMGL acts as a context-specific metabolic and neuroprotective agent, offering the greatest benefits under conditions of metabolic dysfunction. These findings in a preclinical model suggest that targeting early metabolic disturbances provides a testable hypothesis for attenuating AD-related neurodegeneration, though further translational studies are required.