Current Diabetes Reviews - Volume 18, Issue 4, 2022

In this review, we compare major points given in the 2021 American Diabetes Association and the 2020 American Association of Clinical Endocrinologists/American College of Endocrinology guidelines, in particular, the assessment and management of cardiovascular risk in patients with diabetes with a focus on dyslipidemia, blood pressure, and pharmacotherapy in diabetes.

Introduction: Optimal glycemic control is crucial to dental implant long-term functional and esthetic success. Despite HbA1c levels of 7% or lower used is as an indicator for good glycemic control, however, this level may not be attainable for all diabetic patients. Most dentists do not consider patients with poor glycemic control candidates for implant therapy due to higher implant failure, infection or other complications. Aim: This review challenges the concept of one size fits all and aims to critically appraise the evidence for the success or failure rate of dental implants and peri-implant health outcomes in patients with less than optimal glycemic control. Discussion: Evidence suggests that estimating glycemic control from HbA1c measurement alone is misleading. Moreover, elevated preoperative HbA1c was not associated with increased mortality and morbidity after major surgical procedures. Literature for the survival or success of implants in diabetic patients is inconsistent due to a lack of standardized reporting of clinical data collection and outcomes. While a number of studies report that implant treatment in patients with well controlled diabetes has a similar success rate to healthy individuals, other studies suggest that the quality of glycemic control in diabetic patients does not make a difference in the implant failure rate or marginal bone loss. This discrepancy could indicate that risk factors other than hyperglycemia may contribute to the survival of implants in diabetic patients. Conclusion: In the era of personalized medicine, the clinician should utilize individualized information and analyze all risk factors to provide the patient with evidence-based treatment options.

The aim of the present brief review was to discuss carpal tunnel syndrome (CTS) in diabetes mellitus (DM). Generally, CTS is more common in DM, especially in subjects with coexisting diabetic polyneuropathy (DPN) and/or long DM duration. There is no agreement if it is more frequent in type 1 or type 2 DM. The precise underlying mechanisms are not entirely clear but appear to involve hyperglycaemia-induced median nerve oedema, increased sensitivity to exogenous trauma and nerve myelin ischaemia and axonal degeneration. More recently, increased vascular endothelial growth factor (VEGF) and advanced glycation endproducts (AGEs) appear to also play an important role. Median nerve conduction study remains the cornerstone of CTS diagnosis in DM, being more sensitive than clinical examination. CTS can be treated medically or surgically. The latter appears now to be equally effective in subjects with vs. without DM in terms of recurrence rates and quality of life.

Microvascular complications are responsible for a major proportion of the burden associated with diabetes contributing to substantial morbidity, mortality, and healthcare burden in people with diabetes. Retinopathy, nephropathy, and neuropathy constitute the leading causes of blindness, end-stage renal disease, and lower-extremity amputations, respectively. Since the efficacy of causal therapies of diabetic microvascular complications is limited, especially in type 2 diabetes, there is an unmet need for adjunct treatments which should be effective despite ongoing hyperglycemia. Experimental studies have indicated that diabetic microvascular complications can be prevented or ameliorated by various biofactors in animal models by interfering with the pathophysiology of the underlying condition. Some of the findings related to biofactors, like α-lipoic acid and benfotiamine, could be translated into the clinical arena and confirmed in clinical trials, especially in those focusing on diabetic polyneuropathy. Given the micronutrient nature of these compounds, their safety profile is excellent. Thus, they have the potential to favorably modify the natural history of the underlying complication, but long-term clinical trials are required to confirm this notion. Ultimately, biofactors should expand our therapeutic armamentarium against these common, debilitating, and even life-threatening sequelae of diabetes.

Skin involvement is an overlooked aspect in the management of paediatric patients with type 1 diabetes. A comprehensive search of published literature using the PubMed database was carried out using the following key terms: “children,” “pediatric/paediatric patients,” “skin,” “skin disorders,” “type 1 diabetes.” Dermatological side effects are frequently observed among diabetic children and adolescents. Insulin-induced lipodystrophies and allergic contact dermatitis caused by insulin pumps or glycaemic sensors are the most common skin reactions in these patients. Furthermore, several diabetes-associated skin diseases such as necrobiosis lipoidica, granuloma annulare, vitiligo, and bullosis diabeticorum may already be present in paediatric patients. Paediatric diabetes specialists should pay attention to their patients’ skin to recognize these disorders, identify the potential causes, and choose the most suitable treatment. Finally, the evaluation of skin concentrations of advanced glycation end-products using non-invasive diagnostic techniques may be used to assess the risk of chronic complications of diabetes as early as adolescence.

Background: During pregnancy, maintaining an inadequate lifestyle (bad eating habits, stress, consumption of toxic substances, etc.) generates complications such as pre-eclampsia, overweight, lumbar pain and Gestational Diabetes. Objective: This review was carried out with the objective to determine the influence of practising physical activity on the prevention and treatment of Gestational Diabetes; and to evaluate the efficacy of interventions based on therapeutic exercise in the management of such diseases. Method: A systematic review of the publications of the last five years in Medline, Pubmed, Web of Science and Cinahl databases was conducting with the terms Exercise and Gestational Diabetes. Results: 25 articles were found, 9 were observational studies that analysed physical activity habits through questionnaires, and other 16 applied an intervention. With respect to the frequency of the sessions, most of these studies applied their interventions three times per week, with all of them obtaining positive results. Regarding intensity, all the studies that referred to it concluded that it must be at least moderate, highlighting that, at all times, the limitations of pregnant women must be taken into account. Conclusion: Both for the prevention and treatment of this disease, the physical activity must be performed for a minimum of three times per week, at least in moderate intensity, and must be based on aerobic, resistance and strength exercises.

Background: Treatment of diabetes mellitus includes more than one drug of different groups, which may lead to a high pill burden and non-adherence to drugs. We have aimed to systematically analyze the clinical efficacy, safety, and pharmacoeconomic cost-effectiveness of the fixed-dose combination of empagliflozin plus a linagliptin in Type-2 Diabetes mellitus (T2DM) patients. Methods: A literature search of PubMed/MEDLINE, SCOPUS, Google Scholar, and EMBASE was performed using the MeSH terms and/or keywords“((Single-pill combination) OR ((Fixeddose combination) OR (Combination therapy)) AND (Empagliflozin add on-to Linagliptin) OR (Empagliflozin combined with Linagliptin) OR ((Combination of Empagliflozin and Linagliptin)” from the inception to February 2021. Results: Search results were found in a total of 13 clinical studies. After removing duplicates and studies not according to inclusion criteria, a total of eight clinical studies (Randomized controlled trials: 7; Observational cohort studies: 1) were included (n=7491). A significant reduction in the primary endpoint, the mean changes in baseline HbA1c at the end of 24 weeks and/or 52 weeks was found in the empagliflozin plus a linagliptin combination group in all included studies. In addition, significant efficacy was seen in decreasing the secondary endpoints such as the mean change in the fasting plasma glucose, systolic and diastolic blood pressure (DBP), and body weight with fewer adverse events than the adverse effects with either drug alone. Conclusion: After reviewing findings from the available clinical studies of the combination of empagliflozin plus linagliptin, we conclude that the combination is effective, safe, tolerable, and rationale cost effective compared to placebo and either drug alone for the management of T2DM in patients with inadequate glycemic control with metformin alone, patients with intolerance to metformin, increased baseline HbA1c, patients with overweight or obesity and diabetic hypertensive, CHF, atherosclerotic cardiovascular disease, and renal dysfunction patients. Future randomized controlled trials in a larger number of T2DM patients with or without CHF and renal failure patients are recommended.

Background: Diabetes mellitus (DM) and tuberculosis (TB) have been recognized as reemerging epidemics, especially in developing countries. Among all the risk factors, diabetes causes immunosuppression, increasing the risk of active TB three times. Vitamin D has been found as a link between DM-TB co-morbidity. Objective: Vitamin D affects the immune response, suppresses Mycobacterium tuberculosis (Mtb) growth, and affects insulin secretion. The present systematic review determines the effect of vitamin D supplementation on clinical and therapeutic outcomes of DM-TB patients. Method: A comprehensive literature search was carried out in PubMed, Cochrane, Web of Science, and Scopus database to determine eligible studies from inception to January 2021. Out of the 639 articles retrieved, three randomized controlled trials (RCTs) were included in the systematic review. Result: The effect of vitamin D3 or oral cholecalciferol supplementation was assessed on outcomes, such as duration to sputum smear conversion, TB scores improvement, change in glycemic parameters, including HbA1c, FBS, and PLBS, and laboratory parameters, such as Hb, ESR, and CRP. Duration of sputum smear conversion was decreased by two weeks in the vitamin D3 supplemented group in two studies. TB score improvement and changes in glycemic parameters were inclined towards supplemented group; however, they were not significant. Conclusion: The overall effect of vitamin D3 supplementation on TB patients with DM was not significant. Further studies are required in the future examining the effect of supplementation on outcomes in this population.

Background: Cardiovascular autonomic neuropathy (CAN) is a common complication of type 2 Diabetes mellitus (T2D), and prevalence varies according to the methodology used. CAN should be diagnosed in the subclinical stage when an intensive treatment of T2D could avoid the progression to irreversible phases. Objective: Determine the prevalence of early involvement (EI) of CAN in T2D individuals comparing two methodologies. Methods: This was a cross-sectional study that included 183 T2D individuals who were monitored in a Tertiary centre. The diagnosis of CAN was based on the results of four cardiovascular autonomic reflex tests (CARTs: expiration-inspiration index, Valsalva maneuver, orthostatic test, and changes in blood pressure after standing) and of seven heart rate variability (7HRV) indices (CARTs plus the spectral analysis). The findings were validated in an independent cohort comprised of 562 T2D individuals followed in a Primary care setting. Results: With the use of 7HRV, 30.6% and 77.8% of individuals in the Tertiary and in the Primary centers, respectively, were classified as without CAN; 25.1% and 15.3% as EI and 44.3% and 6.9% as definitive CAN, respectively. The use of CARTs decreased the proportion of individuals without CAN in both centers (7.1% and 47%) and increased the frequency of EI (30.6% and 36.6%) and definitive CAN (62.3% and 16.4%), respectively. The concordance between both evaluated methodologies was weak. Conclusion: Higher proportions of T2D individuals were diagnosed with EI and with definitive CAN with the use of CARTs.

Background: Exercise is strongly recommended for the management of type 2 diabetes mellitus (T2DM). However, incomplete intervention reporting in clinical trials limits the replication of exercise protocols. As previously demonstrated by us for exercise and hypertension, the reporting quality might also be insufficient in studies with respect to T2DM and exercise. Objective: The aim of the study was to assess the completeness of exercise intervention reporting in randomized controlled trials (RCTs) for T2DM. Methods: Two independent reviewers applied the Consensus on Exercise Reporting Template (CERT) and the template for intervention description and replication (TIDieR) to 23 exercise trials obtained from the most recent and frequently cited meta-analysis in current guidelines. The completeness of reporting was evaluated, focusing on the F.I.T.T. components (frequency, intensity, time, type). Interrater agreement and associations with publication year and journal impact factor were examined. Results: Mean CERT score was 11/19 (range 5-17), and 8/12 (range 4-12) for TIDieR. F.I.T.T. components were almost completely described, whereas overall completeness of exercise reporting was 60% and 68% (CERT and TIDieR). Replication of each exercise of the respective program was not possible in 52% of interventions. The majority of items had shown excellent agreement. No associations with publication year or impact factor were found. Conclusion: Exercise interventions were not found to be sufficiently reported in RCTs that currently guide clinical practice in T2DM. Replication in further studies or clinical practice is limited due to poor exercise description. We suggest the use of more specific CERT for reporting results of exercise interventions. Further refinement for internal diseases is needed to better describe exercise interventions.