Current Diabetes Reviews - Volume 18, Issue 6, 2022

Background: Magnetic resonance imaging (MRI) is the actual gold standard for the radiological diagnosis of diabetic foot osteomyelitis (DFO). Materials and Methods: MRI is not always available and many patients have contraindications. We evaluated the clinical value of 99mTc-antigranulocyte SPECT/CT (AGS) in eight DFO patients who underwent MRI before. Results: The goal was to have a better clinical view on the extent of bone infection and to ameliorate the surgical approach for DFO. However, this additional scintigraphy did not change anything in the clinical approach. Conclusion: We shared our experience with AGS for clinical management of complex DFO cases.

Diabetic foot ulcer infection is a crucial complication associated with lower-limb amputation and postoperative mortality in individuals with diabetes mellitus. Deciding if a diabetic foot ulcer is infected in a community setting is challenging without validated point-of-care tests. Early detection of infected diabetic foot ulcers can reduce the frequency of hospitalizations, the occurrence of disability, and chances of mortality. Inflammatory biomarkers are predictors of infected diabetic foot ulcers and lower-limb amputation. Procalcitonin, CRP, pentraxin-3, interleukin-6, and calprotectin may help distinguish uninfected from mildly infected diabetic foot ulcers and diagnose soft tissue infections, bone lesions, and sepsis in diabetic patients. Moreover, these biomarkers may be predictors of lower-limb amputation and postoperative mortality. The current management of infected diabetic foot ulcers is disappointing and unsatisfactory, both in preventing its development and halting and modifying its progression. The use of new (molecular) techniques for the identification of the IDFU has not yet to be proven superior to classic cultural techniques for the management of such patients. For clinicians, if the risk stratification of DFU can be obtained earlier in diabetic patients, the hospitalization, disability, and mortality rate will be reduced. For the practical application of these biomarkers, it is important to correlate these quantitative parameters with clinical symptoms. Based on clinical observations and inflammatory biomarker evaluation, it can be used to guide clinical treatment methods. This review details clinical information published during the past several decades and discusses inflammatory biomarkers that may determine the risk and level of infection of diabetic foot ulcers.

Diabetes mellitus is an ailment that affects a large number of individuals worldwide and its pervasiveness has been predicted to increase later on. Every year, billions of dollars are spent globally on diabetes-related health care practices. Contemporary hyperglycemic therapies to rationalize Type 2 Diabetes Mellitus (T2DM) mostly involve pathways that are insulin-dependent and lack effectiveness as the pancreas’ β-cell function declines more significantly. Homeostasis via kidneys emerges as a new and future strategy to minimize T2DM complications. This article covers the reabsorption of glucose mechanism in the kidneys, the functional mechanism of various Sodium- Glucose Cotransporter 2 (SGLT2) inhibitors, their structure and driving profile, and a few SGLT2 inhibitors now accessible in the market as well as those in different periods of advancement. The advantages of SGLT2 inhibitors are dose-dependent glycemic regulation changes with a significant reduction both in the concentration of HbA1c and body weight clinically and statistically. A considerable number of SGLT2 inhibitors have been approved by the FDA, while a few others, still in preliminaries, have shown interesting effects.

Undeniably, lipid plays an extremely important role in the homeostasis balance since lipid contributes to the regulation of the metabolic processes. The metabolic syndrome pathogenesis is multi-pathway that composes neurohormonal disorders, endothelial cell dysfunction, metabolic disturbance, genetic predisposition, in addition to gut commensal microbiota. The heterogenicity of the possible mechanisms gives the metabolic syndrome its complexity and limitation of therapeutic accesses. The main pathological link is that lipid contributes to the emergence of metabolic syndrome via central obesity and visceral obesity that consequently lead to oxidative stress and chronic inflammatory response promotion. Physiologically, a balance is kept between the adiponectin and adipokines levels to maintain the lipid level in the organism. Clinically, extremely important to define the borders of the lipid level in which the pathogenesis of the metabolic syndrome is reversible, otherwise it will be accompanied by irreversible complications and sequelae of the metabolic syndrome (cardiovascular, insulin resistance). The present paper is dedicated to providing novel insights into the role of lipid in the development of metabolic syndrome; hence dyslipidemia is the initiator of insulin resistance syndrome (metabolic syndrome).

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.

Background: It is essential for randomized controlled trials (RCTs) to report results in a comprehensive manner. Hence, it is necessary to assess the robustness of the trials with statistically significant and as well as non-significant results. Robustness can be evaluated using fragility index (FI), while reverse fragility index (RFI) can be used for trials with statistically significant as well as non-significant results. The primary aim of this study was to calculate FI and RFI for cardiovascular outcome trials (CVOT). Materials and Methods: PubMed/MEDLINE was searched to identify all RCTs of antidiabetic drugs where the primary objective was to evaluate the cardiovascular outcomes. We recorded the trial characteristics of each CVOT trial. The FI, RFI, fragility quotient (FQ), and reverse fragility quotient (RFQ) were calculated to evaluate the robustness of the trials. Spearman rank correlation test was used for correlation. Findings: A total of 889 studies were identified and 24 RCTs were included. Among the 24 trials, 12 (50%) trials achieved statistical significance. The median FI and RFI were 29 (4-12) and 22.5 (1-37) for trials with statistically significant and non-significant results. The median FQ and RFQ were 0.0075 (0.002-0.013) and 0.0003 (0.0001-0.004) for trials with statistically significant and non-significant results. The hazard ratio, p-value, and NNT-B had a strong negative relationship with FI. Interpretation: Our study showed that half of the trials showing the superiority of cardioprotective benefits have favourable FI. The trials that failed to show superiority also have a reasonable RFI indicating the robustness of these trials. However, the results of the trials where patients lost to follow- up exceed the FI of that trial demands caution during interpretation.

Background: Diabetes mellitus is the most common metabolic alteration in gestation. Monogenic diabetes or Maturity-Onset Diabetes of the Young (MODY) is a subtype caused by a primary defect in insulin secretion determined by autosomal dominant inheritance. Objectives: This study aimed to analyze molecular changes of the Glucokinase gene (GCK) in pregnant women with hyperglycemia during gestation and in their neonates. Case Study and Methods: We collected 201 blood samples, 128 from pregnant patients diagnosed with hyperglycemia and 73 from umbilical cord blood from neonates of the respective patients. DNA extraction and polymerase chain reaction (PCR) were performed to identify molecular changes in the GCK gene. Results: In a total of 201 samples (128 from mothers and 73 from neonates), we found changes in 21 (10.6%), among which 12 were maternal samples (6.0%) and 9 were neonatal samples (4.5%). DNA sequencing identified two polymorphisms and one deleterious MODY GCK-diagnostic mutation. Conclusion: The prevalence of molecular changes in the Glucokinase gene (GCK) and the deleterious MODY GCK-diagnostic mutation were 9.3% and 0.7%, respectively, in women with hyperglycemia during gestation and 12.5% and 1.3%, respectively, in their neonates. The deleterious MODY GCK mutation identified is associated with a reduction in GCK activity and hyperglycemia. In the other molecular changes identified, it was impossible to exclude phenotypic change despite not having clinical significance. Therefore, these changes may interfere with the management and clinical outcome of the patients.

Background: Diabetic Foot Disease (DFD) is more prevalent among males and is associated with an excess risk of cardiovascular events or mortality. Aims: This study aimed at exploring the risk of cardiovascular events, renal failure, and all-cause mortality after incident DFD hospitalizations, separately in males and females, to detect any gender difference in a cohort of 322,140 people with diabetes retrospectively followed up through administrative data sources in Tuscany, Italy, over the years 2011-2018. Methods: The Hazard Ratio (HR) for incident adverse outcomes after first hospitalizations for DFD, categorized as major/minor amputations (No.=449;3.89%), lower limbs’ revascularizations (LLR: No.=2854;24.75%), and lower-extremity-arterial-disease (LEAD) with no procedures (LEAD-no proc: No.=6282;54.49%), was compared to the risk of patients having a background of DFD (ulcers, infections, Charcot-neuroarthropathy: No.=1,944;16.86%). Results: DFD incidence rate was higher among males compared to females (1.57(95% CI:1.54-1.61) vs. 0.97(0.94-1.00)/100,000p-years]. After DFD, the overall risk of coronary artery disease was significantly associated with the male gender and of stroke with the female gender. LEAD-no proc and LLR were associated with the risk of stroke only in females, whereas they were found to be associated with the risk of coronary artery disease among females to a significantly greater extent compared to males. The incident of renal failure was not associated with any DFD category. Amputations and LEAD-no proc significantly predicted high mortality risk only in females, while LLR showed reduced risk in both genders. Moreover, females had a greater risk of composite outcomes (death or cardiovascular events). Compared to the background of DFD, the risk was found to be 34% higher after amputations (HR: 1.34(1.04-1.72)) and 10% higher after LEAD-no proc (HR:1.10(1.03-1.18)), confirming that after incident DFD associated with vascular pathogenesis, females are at an increased risk of adverse events. Conclusion: After incident DFD hospitalizations, females with DFD associated with amputations or arterial disease are at a greater risk of subsequent adverse cardiovascular events than those with a DFD background.

Purpose: This study aimed to analyze the effect of a Pilates protocol on respiratory muscle strength and heart rate variability (HRV) in patients with type 2 diabetes. Method: A randomized clinical trial (RBR-2gc2qj) was conducted on a type 2 diabetic target population. Patients practiced the Pilates protocol for 8 weeks, with two visits per week. The variables tested were maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), and HRV (time and frequency domains). All variables were tested for normal distribution. Using SPSS 21.0, analysis of variance was performed for variables with normal distribution, and the Wilcoxon and Friedman tests were used for variables that did not show a normal distribution, with a 5% significance level. Results: Forty-four participants were included in the study (intervention group: 22; control group: 22; mean age: 61.23 ± 8.49 years), most of whom were female (77.3%), married or in a consensual union (59.1%), had complete literacy (31.8%), and had an average body mass index of 26.96 ± 4.35 kg/m². There were no significant differences in MIP and MEP before and after the protocol between the intervention and control groups. Regarding HRV, there were significant differences in autonomic modulation, especially between the moments before and during exercise and between the moments during and after exercise; however, it was not possible to determine which system (sympathetic or parasympathetic) is most involved in these changes. Conclusion: The exercise protocol based on the Pilates method did not alter respiratory muscle strength but promoted changes in HRV, especially between the moments before and during exercise and during and after exercise.

Background and Aim: Surgical and endovascular revascularization procedures along with hyperbaric oxygen therapy (HBOT) and topical oxygen therapy (TOT) for chronic oxygen-deprived wounds are standard care treatment protocols for diabetic foot ulcer (DFU). Topical developments in the delivery of topical oxygen therapy have made this a more feasible treatment in practice. The present case series highlights the efficacy of NATROX therapy as TOT in wound healing and the impact of increased oxygenation on ulcer healing in patients with diabetic foot ulcers. Methods: The TOT was evaluated in 6 patients with DFU who have applied NATROX topical oxygen delivery system for a period ranging from 6 weeks to 24 weeks at Kahel Specialized Centre, located in Olaya, Riyadh, Saudi Arabia. Results: The administration of TOT demonstrated complete wound healing in all the six patients who either had ulcers with minor amputation of toes/heel or had ulcers with other comorbidities in a range from 3 to 8 weeks. Conclusion: NATROX therapy is an advanced topical oxygen delivery system compared to other conventional oxygen delivery systems; however, the study warrants further research to assess its potential applicability in DFU wound healing in large sample size and across the races.