Current pharmacological treatment of painful diabetic neuropathy: A narrative review

Background and Objectives: Distal symmetrical polyneuropathy (DSPN) is one of the most common chronic complications of diabetes mellitus. Although it is usually characterized by progressive sensory loss, some patients may develop chronic pain. Assessment of DSPN is not difficult, but the biggest challenge is making the correct diagnosis and choosing the right treatment. The treatment of DSPN has three primary objectives: glycemic control, pathogenic mechanisms, and pain management. The aim of this brief narrative review is to summarize the current pharmacological treatment of painful DSPN. It also summarizes knowledge on pathogenesis-oriented therapy, which is generally overlooked in many publications and guidelines. Materials and Methods: The present review reports the relevant information available on DSPN treatment. The search was performed on PubMed, Cochrane, Semantic Scholar, Medline, Scopus, and Cochrane Library databases, including among others the terms “distal symmetrical polyneuropathy”, “neuropathic pain treatment”, “diabetic neuropathy”, “diabetes complications”, ”glycaemic control”, “antidepressants”, “opioids”, and “anticonvulsants”. Results: First-line drugs include antidepressants (selective serotonin reuptake inhibitors and tricyclic antidepressants) and pregabalin. Second- and third-line drugs include opioids and topical analgesics. While potentially effective in the treatment of neuropathic pain, opioids are not considered to be the first choice because of adverse reactions and addiction concerns. Conclusions: DSPN is a common complication in patients with diabetes, and severely affects the quality of life of these patients. Although multiple therapies are available, the guidelines and recommendations regarding the treatment of diabetic neuropathy have failed to offer a unitary consensus, which often hinders the therapeutic options in clinical practice

Experimental and Emerging Free Fatty Acid Receptor Agonists for the Treatment of Type 2 Diabetes

The current management of Type 2 Diabetes Mellitus (T2DM) includes incretin-based treatments able to enhance insulin secretion and peripheral insulin sensitivity as well as improve body mass, inflammation, plasma lipids, blood pressure, and cardiovascular outcomes. Dietary Free Fatty Acids (FFA) regulate metabolic and anti-inflammatory processes through their action on incretins. Selective synthetic ligands for FFA1-4 receptors have been developed as potential treatments for T2DM. To comprehensively review the available evidence for the potential role of FFA receptor agonists in the treatment of T2DM, we performed an electronic database search assessing the association between FFAs, T2DM, inflammation, and incretins. Evidence indicates that FFA1-4 agonism increases insulin sensitivity, induces body mass loss, reduces inflammation, and has beneficial metabolic effects. There is a strong inter-relationship between FFAs and incretins. FFA receptor agonism represents a potential target for the treatment of T2DM and may provide an avenue for the management of cardiometabolic risk in susceptible individuals. Further research promises to shed more light on this emerging topic

Phosphorus nutritional knowledge among dialysis health care providers and patients: a multicenter observational study

Background-aims Phosphorus nutritional knowledge level of hemodialysis patients and renal nurses has been found to be low, while respective knowledge of nephrologists has not been studied yet. There are equivocal results regarding the association of phosphorus nutritional knowledge level and serum phosphorus values. The aim of this study was to assess phosphorus nutritional knowledge of hemodialysis patients, nephrologists and renal nurses and seek potential interventions to improve patients’ adherence to phosphorus and overall nutritional guidelines. Methods This cross-sectional observational study was conducted on sixty eight hemodialysis patients, 19 renal nurses and 11 nephrologists who were recruited from 3 hemodialysis units in Greece. Phosphorus nutritional knowledge of the participants was assessed by a 25-item item questionnaire (CKDKAT–N) which included 15 questions on phosphorus and 10 questions on protein, sodium, and potassium knowledge. Results Nephrologists had higher CKDKAT–N total (19.1 ± 3.6 vs 14.1 ± 2.8 and 13.2 ± 2.8, P < 0.01) and phosphorus knowledge scores (10.6 ± 2.7 vs 7.6 ± 2.2 and 7.3 ± 2.0, P < 0.01) compared to renal nurses and patients respectively. There were no differences in total and phosphorus knowledge scores between nurses and patients. Patients and nurses answered correctly significantly less questions regarding phosphorus compared with the rest of the questions (P < 0.01) while no such difference was found in nephrologists. Serum phosphorus was positively correlated with phosphorus knowledge score (r = 0.31, P = 0.02), and negatively correlated with patient age (r = −0.34, P < 0.05). None of the patients, 11% of the nurses and 27% of the nephrologists answered correctly all three questions regarding P, K and Na dietary recommendations (P < 0.01). Conclusions The study confirms that hemodialysis patients have low renal nutrition knowledge while higher nutritional phosphorus knowledge does not lead to lower serum phosphorus values. Alarmingly, renal nurses have been found to have a similar level of knowledge with hemodialysis patients, something that needs to be taken into account when training the new dialysis staff. Nephrologists have superior knowledge; however they are still lacking essential nutritional knowledge that could affect patients' and nurses’ overall understanding. Continuing education on nutrition of nephrologists and renal nurses could improve nutrition care of hemodialysis patients

Metabolic disorders during pregnancy and postpartum cardiometabolic risk

Hormonal changes during pregnancy can trigger gestational diabetes (GDM), which is constantly increasing. Its main characteristic is pronounced insulin resistance, but it appears to be a multifactorial process involving several metabolic factors; taken together, the latter leads to silent or clinically evident cardiovascular (CV) events. Insulin resistance and central adiposity are of crucial importance in the development of metabolic syndrome, and they appear to correlate with CV risk factors, including hypertension and atherogenic dyslipidaemia. Hypertensive disease of pregnancy (HDP) is more likely to be an accompanying co-morbidity in pregnancies complicated with GDM. There is still inconsistent evidence as to whether or not co-existent GDM and HDP have a synergistic effects on postpartum risk of cardiometabolic disease; however, this synergism is becoming more accepted since both these conditions may promote endothelial inflammation and early atherosclerosis. Regardless of the presence or absence of the synergism between GDM and HDP, these conditions need to be dealt early enough, in order to reduce CV morbidity and to improve health outcomes for both women and their offspring

CARDIORESPIRATORY CHARACTERISTICS AND CHOLESTEROL RESPONSES TO A SINGLE SESSION OF HEAVY LEG PRESS EXERCISE

The effect of resistance exercise on blood lipids is not clear yet. The purpose of this study was to examine the cholesterol responses to a heavy resistance leg press exercise emphasizing on the eccentric movement 24 and 48 hours following exercise and to quantify the cardiorespiratory responses of the exercise bout in an attempt to clarify the exercise characteristics that may be responsible for the effects of heavy resistance exercise on blood lipids. Nine healthy, untrained male volunteers aged 27.2 ± 1.1 yrs (76.2 ± 2.5 kg, 1.79 ± 0.02 m) performed a session of heavy RE emphasizing on the eccentric movement consisting of eight sets of inclined leg presses at six repetition maximum with 3-min rest intervals. Venous blood samples were obtained at rest (control) and 24 and 48 hours following exercise. Average VO2 at rest was 4.0 ± 0.4 ml·min-1·kg-1, during exercise 19.6 ± 0.2 ml·min-1·kg-1 and during the 180 sec recovery period between sets 12.5 ± 0.2 ml·min-1·kg-1. RER values decreased with the progression of the exercise and were significantly lower during the last four sets compared with the first four sets of the exercise session. Resting heart rate was 67 ± 2 bpm, and maximum heart rate during exercise was 168 ± 1 bpm. Serum creatine kinase was significantly elevated on day 1 (1090 ± 272 U·L-1, p < 0.03) and peaked on day 2 (1230 ± 440 U·L-1 p < 0. 01). Total cholesterol, HDL cholesterol and calculated LDL cholesterol concentration did not change significantly following with exercise. This protocol of heavy resistance exercise has no effect on TC or cholesterol sub-fraction concentration 24 and 48 hours following exercise which may be due to the low energy expenditure of the exercise and/or to the gender of the participant

Advances in pharmacological treatment of type 1 diabetes during pregnancy

Introduction: In women with type 1 diabetes mellitus (T1DM), pregnancy is associated with a potential risk of maternal, foetal and neonatal outcomes. Stringent metabolic control is required to improve these outcomes. Areas covered: In this review, the authors summarise the current evidence from studies on the pharmacological therapy and on monitoring of T1DM during pregnancy. The authors also discuss the use of new technologies to improve therapeutic management and patient compliance. Expert opinion: Pre-conception counselling is essential in T1DM to minimise pregnancy risks. Pregnancy in T1DM is always considered a high-risk pregnancy. During pregnancy, the target haemoglobin A1C (HbA1c) is near-normal at &lt;6%, without excessive hypoglycaemia. Strict control of pre- and post-prandial glucose is also required. Human soluble insulin, neutral protamine Hagedorn and the quick-acting insulin analogues aspart and lispro are widely used. Insulin is administered either as a basal-bolus regimen or by continuous subcutaneous insulin infusion. Careful and strict glucose monitoring is also needed during labour and delivery, including caesarean section. Moreover, the control of retinopathy, hypertension, nephropathy, hyper- and hypothyroidism is required. Post-partum, insulin requirements decrease, and less stringent glycaemic control is pursued, to avoid hypoglycaemias. Finally, breastfeeding is recommended and should be encouraged

Non-alcoholic fatty liver disease through the female lifespan: the role of sex hormones

The prevalence of non-alcoholic fatty liver disease (NAFLD) differs between various stages of the female lifespan. The aim of this review is to summarize current evidence on the association of NAFLD and circulating sex hormones and to explore the pathogenesis of NAFLD within the context of (1) sex hormone changes during the reproductive, post-reproductive female life and beyond and (2) the in vitro and in vivo evidence on pharmacological modulation in women on menopausal hormone treatment (MHT) or endocrine therapy after breast cancer. The fluctuation in estrogen concentrations, the relative androgen excess, and the age-related reduction in sex hormone-binding globulin are related to increased NAFLD risk. Moreover, the peri-menopausal changes in body composition and insulin resistance might contribute to the increased NAFLD risk. Whether MHT prevents or improves NAFLD in this population remains an open question. Studies in women with breast cancer treated with tamoxifen or non-steroidal aromatase inhibitors point to their adverse effects on NAFLD development, although a more pronounced effect of tamoxifen is reported. Future studies focusing on the underlying pathogenesis should identify subgroups with the highest risk of NAFLD development and progression into more aggressive forms, as well as elucidate the role of hormone therapies, such as MHT. © 2022, The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE)

Pharmacotherapy for gestational diabetes

Introduction: Gestational diabetes mellitus (GDM) represents impaired carbohydrate metabolism during pregnancy and is characterized by progressive insulin resistance and compensatory hyperinsulinaemia. If inadequately treated, it may lead to fetal macrosomia and other adverse outcomes. Areas covered: In this review, the authors summarize the current evidence from studies on the use of insulin and other agents for the treatment of women with GDM. Expert opinion: Lifestyle management is of paramount importance for the treatment of GDM. In pharmacotherapy, insulin remains the long-established mainstay of treatment. NPH (Neutral Protamine Hagedorn) and soluble human insulin have long been established for use, but favorable experience has now also accumulated with the newer insulins (aspart, lispro, detemir). Alternatively, metformin and glyburide have been used in GDM, but they have never gained wide acceptance. Nutritional supplements based on micronutrients and bioactives (probiotics and myoinositol) have shown promising results as well. Further experience with incretin agents (DPP-4 inhibitors and GLP-1 receptor agonists) is awaited