Secondary diabetes mellitus in pheochromocytomas and paragangliomas.

Secondary diabetes mellitus (DM) in secretory pheochromocytomas and paragangliomas (PPGLs) is encountered in up to 50% of cases, with its presentation ranging from mild, insulin resistant forms to profound insulin deficiency states, such as diabetic ketoacidosis and hyperglycemic hyperosmolar state. PPGLs represent hypermetabolic states, in which adrenaline and noradrenaline induce insulin resistance in target tissues characterized by aerobic glycolysis, excessive lipolysis, altered adipokine expression, subclinical inflammation, as well as enhanced gluconeogenesis and glucogenolysis. These effects are mediated both directly, upon adrenergic receptor stimulation, and indirectly, via increased glucagon secretion. Impaired insulin secretion is the principal pathogenetic mechanism of secondary DM in this setting; yet, this is relevant for tumors with adrenergic phenotype, arising from direct inhibitory actions in beta pancreatic cells and incretin effect impairment. In contrast, insulin secretion might be enhanced in tumors with noradrenergic phenotype. This dimorphic effect might correspond to two distinct glycemic phenotypes, with predominant insulin resistance and insulin deficiency respectively. Secondary DM improves substantially post-surgery, with up to 80% remission rate. The fact that surgical treatment of PPGLs restores insulin sensitivity and secretion at greater extent compared to alpha and beta blockade, implies the existence of further, non-adrenergic mechanisms, possibly involving other hormonal co-secretion by these tumors. DM management in PPGLs is scarcely studied. The efficacy and safety of newer anti-diabetic medications, such as glucagon-like peptide 1 receptor agonists and sodium glucose cotransporter 2 inhibitors (SGLT2is), as well as potential disease-modifying roles of metformin and SGLT2is warrant further investigation in future studies.

Relationship between Short- and Mid-Term Glucose Variability and Blood Pressure Profile Parameters: A Scoping Review.

Background. Increased variability of glucose (GV) and blood pressure (BPV) is linked to a higher risk of macro- and microvascular complications and other hard endpoints. This scoping review aims to summarize the existing evidence regarding the association between the parameters of the blood pressure (BP) profile, especially BPV, with indices of short- and mid-term GV. Methods. A literature search was conducted in the MEDLINE/PubMed, Cochrane, Embase, Web of Science, and Wiley Online Library databases. Results. The main findings of this review are as follows: (i) 13 studies were included, mainly with small sample sizes; (ii) there was a considerable degree of heterogeneity in the characteristics of the study participants (age range, individuals with normoglycemia, type 1 or 2 diabetes, normal BP, or hypertension), as well as in the methodologies (mainly in terms of the duration of the data collection period) and variability indices examined (mean amplitude of glycemic excursions and coefficient of glucose variation most frequently reported); and (iii) the results were heterogeneous regarding the association between GV and the parameters of the BP profile. Conclusions. There is a significant lack of evidence on the association between GV and BPV. Future research implementing a standardized methodology should focus on the determinants, association, and clinical relevance of GV and BPV.

Effects of Alpha-lipoic Acid Supplementation on Human Diabetic Nephropathy: A Systematic Review and Meta-analysis.

BACKGROUND: Diabetic nephropathy (DN) is kidney dysfunction, which occurs due to elevated urine albumin excretion rate and reduced glomerular filtration rate. Studies on animals have shown that alpha-lipoic acid (ALA) supplementation can reduce the development of DN. OBJECTIVES: We performed a systematic review and meta-analysis to examine the effects of ALA supplementation on biological indices (albumin, creatinine, etc.) indicative of human DN. METHODS: The search procedure included PubMed Central, Embase, Cochrane Library (trials), and Web of Science (protocol registration: INPLASY202060095). RESULTS: We found that ALA supplementation decreased 24h urine albumin excretion rate in patients with diabetes (standardized mean difference=-2.27; confidence interval (CI)=(-4.09)-(-0.45); I2=98%; Z=2.44; p=0.01). A subgroup analysis revealed that the results of studies examining only ALA did not differ from those examined ALA in combination with additional medicines (Chisquared= 0.19; p=0.66; I2=0%), while neither ALA nor ALA plus medication had an effect on 24h urine albumin excretion rate (p>0.05). Also, ALA supplementation decreased urine albumin mg/l (mean difference (MD)=-12.95; CI=(-23.88)-(-2.02); I2=44%; Z=2.32; p=0.02) and urine albumin to creatinine ratio (MD=-26.96; CI=(-35.25)-(-18.67); I2=0%; Z=6.37; p<0.01) in patients with diabetes. When the studies examining ALA plus medication were excluded, it was found that ALA supplementation had no effect on urine albumin mg/l (p>0.05) but did significantly decrease urine albumin to creatinine ratio (MD=-25.88, CI=(34.40-(-17.36), I2=0%, Z=5.95, p<0.00001). CONCLUSION: The available evidence suggests that ALA supplementation does not improve biological indices that reflect DN in humans. Overall, we identified limited evidence, and therefore, the outcomes should be considered with caution.