Current Diabetes Reviews - Volume 18, Issue 1, 2022

Background: Diabetes mellitus (DM), one of the worldwide leading causes of death, is associated with a plethora of micro- and macro-vascular complications which should be carefully investigated and, in case, treated in order to improve quality of life and reduce the risk of premature mortality. Objective: The study aimed to investigate and report current evidence with regard to the association between sexual dysfunction and diabetes. Methods: A detailed analysis of current literature has been performed on PubMed and Scholar in order to retrieve the most relevant findings pertaining to the study topic. Results: Female and male sexual dysfunction often occurs in diabetes; while cardiovascular complications are clearly involved, psychosexological factors, endocrine complications, and endothelial dysfunction all contribute to the pathogenesis of sexual dysfunctions. Psychological symptoms are seldom investigated, yet they should not be overlooked by the clinician; in fact, an interplay between sexual dysfunctions and depressive symptoms has been reported, and beneficial effects in both conditions might be obtained by adequate psychological support. Sexual dysfunctions can also act as early biomarkers of cardiovascular disease, a phenomenon frequently reported in men, in which erectile dysfunction predicts the development of coronary artery disease. Additionally, drug therapies can act in both directions, with treatments for diabetes possibly improving male sexual function and exerting beneficial effects for cardiovascular health being reported for pro-erectile drugs. Conclusion: Sexual dysfunctions often occur in men and women with diabetes. Investigating micro- and macro-vascular complications might not be enough to prevent the development or worsening of any sexual dysfunction; endocrine and psychological assessments are therefore needed to provide the best chances for adequate treatment.

Background: Although hyperglycaemia is known to be the leading cause of diabetic complications, the beneficial effect of optimal glucose control in preventing diabetic complications is still far from being proven. In fact, such complications may not be related to glycaemic control alone. Objective: This review summarizes several studies that suggest that a C-peptide deficiency could be new and common pathophysiology for complications in type 1 diabetes, including sexual and reproductive dysfunction. Methods: We reviewed in vitro, in vivo, and human studies on the association between C-peptide deficiency or C-peptide replacement therapy and complications in type 1 diabetes. It seems that Cpeptide replacement therapy may interrupt the connection between diabetes and sexual/reproductive dysfunction. Results: The Diabetes Control and Complications Trial suggested that maintaining C-peptide secretion is associated with a reduced incidence of retinopathy, nephropathy, and hypoglycaemia. Risk of vascular, hormonal, and neurologic damage in the structures supplying blood to the penis increases with increasing levels of HbA1. However, several human studies have suggested an association between C-peptide production and hypothalamic/pituitary functions. When exposed to C-peptide, cavernosal smooth muscle cells increase the production of nitric oxide. C-peptide in diabetic rats improves sperm count, sperm motility, testosterone levels, and nerve conduction compared to non-treated diabetic rats. Conclusion: C-peptide deficiency may be involved, at least partially, in the development of several pathological features associated with type 1 diabetes, including sexual/reproductive dysfunction. Preliminary studies have reported that C-peptide administration protects against diabetic microand macrovascular damages as well as sexual/reproductive dysfunction. Therefore, further studies are needed to confirm these promising findings.

Female sexual dysfunction (FSD) is an underinvestigated comorbidity of diabetes mellitus, often not evaluated in diabetes clinics. Diabetic women should be encouraged to talk about this topic by their diabetologist, because these problems could be comorbid to cardio-metabolic alterations, as it happens in the male counterpart. This review summarizes evidence on sexual dysfunction characteristics in diabetic women, exploring possible underlying pathogenic mechanisms. The role of hypoglycemic drugs in this context was also evaluated. To date, no specific questionnaire has been designed for the assessment of sexual dysfunctions in diabetic female patients but the use of colour-doppler ultrasound of clitoral arteries has been highlighted as a useful tool for the assessment of cardiovascular risk in these women. Similarly, no specific guidelines are available for the treatment of FSD in the diabetic population but patients should be supported to have a healthy lifestyle and, in the absence of contraindications, can benefit from already approved treatments for FSD.

The prevalence of obesity has dramatically increased all over the world. Body mass index (BMI) has been used as the most common available measure to determining obesity status. While the site of excessive fat mass accumulation is a stronger determinant of cardio-metabolic complication, with respect to systemic and generalized obesity, which is only determined through BMI. So, it is concluded that using traditional anthropometric indices such as BMI for interpreting the obesity status and cardio-metabolic risk has considerable limitations. Thus, the main aims of the present study are to discuss possible drawbacks of anthropometric indices especially BMI, which in epidemiological studies are usually neglected, as well as lend important consideration to using other anthropometric indices such as measurement of obesity and related cardio-metabolic complications with a special emphasis on the use of waist circumference, waist-to-hip ratio and waist-to-height ratio.

Despite the advent of novel therapies which manage and control diabetes well, the increased risk of morbidity and mortality in diabetic subjects is associated with the devastating secondary complications it produces. Long-standing diabetes majorly drives cellular and molecular alterations, which eventually damage both small and large blood vessels. The complications are prevalent both in type I and type II diabetic subjects. The microvascular complications include diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, while the macrovascular complications include diabetic heart disease and stroke. The current therapeutic strategy alleviates the complications to some extent but does not cure or prevent them. Also, the recent clinical trial outcomes in this field are disappointing. Success in the drug discovery of diabetic complications may be achieved by a better understanding of the underlying pathophysiology and by recognising the crucial factors contributing to the development and progression of the disease. In this review, we discuss the well-studied cellular mechanisms leading to the development and progression of diabetic complications. In addition, we also highlight the various therapeutic paradigms currently in clinical practice.

Diabetes mellitus is a chronic illness with a variety of causes and pathophysiology. For the management of diabetes, various synthetic antidiabetic drugs are available. Still, people prefer complementary and alternative therapies as well as traditional herbal home remedies because they are perceived to be free of side effects and generally recognized as safe due to their natural origin. Hence, worldwide, the majority of the population is consuming herbs and/or herbal products in their daily routine. It has been observed that individuals with diabetes also consume herbs/herbal products either with or without medical supervision. This co-consumption of antidiabetic medications and herb/herbal products may result in herb-drug interactions, which might be potentially beneficial or harmful or, in some cases, even fatal. Most of the times, these interactions remain unnoticed or undiagnosed due to lack of knowledge and awareness about them. In this review, the authors have summarized some important aspects related to the herb-drug interaction (HDI), which include methods for prediction and mechanism of HDI (pharmacokinetic and pharmacodynamic) and also the clinical and experimental literature on herb-drug interactions (HDI) in the treatment of diabetes. Authors have attempted to categorize the interactions between oral hypoglycemic agents and various herbs as beneficial or harmful based on the results reported in the original research work.

Background: Type 2 diabetes mellitus (T2DM) is an ever-growing epidemic in India and poses significant morbidity, mortality, and socioeconomic burden. Introduction: Growth differentiation factor-15 (GDF15) is a stress-responsive cytokine, increased in T2DM patients compared to control subjects without the disease. We aimed to assess whether serum GDF15 and adipose tissue GDF15 expression can differentiate between obese pre-diabetes and T2DM and control populations. Methodology: We recruited 156 individuals including 73 type 2 diabetes, 30 pre-diabetes, and 53 healthy controls. Clinical history, anthropometric measurements and biochemical profiling were taken. Insulin resistance indices were calculated following HOMA models. Serum GDF15 was measured by sandwich ELISA. Visceral adipose tissue (VAT) expression of GDF15 was observed in 17 T2DM patients and 29 controls using SYBR Green chemistry in RT-PCR using GAPDH as the housekeeping gene. The data were analyzed on R programming platform using RStudio. Results: Serum GDF15 was significantly higher (p<0.001) in T2DM subjects (median 1445.47 pg/mL) compared to pre-diabetes (627.85 pg/mL) and healthy controls (609.01 pg/mL). Using the ΔΔCt method, the VAT GDF15 expression was 1.54 fold and 1.57 fold upregulated in T2DM (n=17) compared to control subjects (n=29), and obese (n=12) compared to non-obese (n=34)subjects, respectively. The optimal cut-off point following Youden’s index method was found to be 868.09 pg/mL. ROC curve analysis revealed that serum GDF15 had a sensitivity, specificity, and area under the curve (AUC) of 90.41%, 79.52%, and 0.892 respectively. GDF15 levels were significantly associated with age, BMI, HbA1c, fasting blood sugar, and insulin resistance indices. Conclusion: Hence, serum GDF15 is a biomarker for T2DM patients in our study population from Western India. However, larger prospective cohorts are necessary to validate this claim.

Background: Some authors evaluated the effect of VD on hyperglycemia in T1DM, but the results remain controversial. This study aims to analyze the effects of high-dose VD supplementation on T1DM patients’ glycemic levels, maintaining stable doses of insulin. Methods: Prospective, 12-week clinical trial including 67 T1DM patients, supplemented with high doses of cholecalciferol according to participants' VD value. Patients with VD levels below 30 ng/mL received 10,000 IU/day; those with levels between 30-60 ng/mL received 4,000 IU/day. Patients who had not achieved 25(OH)D levels > 30 ng/ml or presented insulin dose variation during the study were not analyzed. Results: Only 46 out of 67 patients accomplished the criteria at the end of the study. There was no general improvement in the glycemic control evaluated by HbA1c (9.4 ± 2.4 vs 9.4 ± 2.6, p=NS) after VD supplementation. However, a post-hoc analysis, based on HbA1c variation, identified patients who had HbA1c reduced at least 0.6% (group 1, N = 13 (28%)). In addition, a correlation between 25(OH)D levels with HbA1c and total insulin dose at the end of the study was observed (r = -0.3, p<0.05; r=-0.4, p<0.05, respectively), and a regression model demonstrated that 25(OH)D was independent of BMI, duration of T1DM and final total insulin dose, being capable of determining 9.2% of HbA1c final levels (Unstandardized B coefficient = −0.033 (CI 95%: −0.064 to −0.002), r² = 0.1, p <0.05). Conclusion: Our data suggest that VD is not widely recommended for glycemic control. Nevertheless, specific patients might benefit from this approach.

Aim: This study aims to identify the epidemiological and social characteristics of the diabetic population in French Guiana. Background: The prevalence of diabetes is very high in the French overseas departments. French Guiana is, however, a very atypical territory, closer in the epidemiological field to Latin America than European and French standards. Objective: To perform a descriptive analysis of variables related to renouncing medical care, social parameters, and use of healthcare services. Methods: A two-stage random sample of 1390 individuals aged 30 to 75 years was surveyed by telephone, and screening was initially done for diabetic versus non-diabetic individuals. Logistic regression was fitted on the sample to adjust for potential confounding factors. A Kaplan-Meier analysis showed the risk of diabetes as a function of the age of onset. Results: The prevalence rate of diabetes was 9.3%, particularly among women, for whom 20% had a history of gestational diabetes. Excess weight and obesity were found in 60% of people with diabetes. The diabetic individuals in French Guiana were younger than those in mainland France, and 30% of people with diabetes were on insulin. They often reported sleep problems, and their health status was described as poor. People with diabetes did not regularly consult a doctor and were very rarely followed up by a specialist. Conclusions: The prevalence rate of diabetes and obesity in French Guiana was one of the highest among the French territories, with specific vulnerabilities requiring to be addressed by local health policies.

Aim: Examine bile acids effects in Type 2 diabetes. Background: In recent studies, the bile acid ursodeoxycholic acid (UDCA) has shown potent antiinflammatory effects in obese patients while in type 2 diabetics (T2D) levels of the pro-inflammatory bile acid lithocholic acid were increased, and levels of the anti-inflammatory bile acid chenodeoxycholic acid were decreased, in plasma. Objective: Hence, this study aimed to examine applications of novel UDCA microparticles in diabetes. Methods: Diabetic balb/c adult mice were divided into three equal groups and gavaged daily with either empty microcapsules, free UDCA, or microencapsulated UDCA over two weeks. Their blood, tissues, urine, and faeces were collected for blood glucose, inflammation, and bile acid analyses. UDCA resulted in modulatory effects on bile acids profile without antidiabetic effects suggesting that bile acid modulation was not directly linked to diabetes treatment. Results: UDCA resulted in modulatory effects on bile acids profile without antidiabetic effects suggesting that bile acid modulation was not directly linked to diabetes treatment. Conclusion: Bile acids modulated the bile profile without affecting blood glucose levels.