Current Diabetes Reviews - Volume 15, Issue 6, 2019

Background: The potential influence of pregnancy and parity on the risk of chronic diabetic complications is a matter of great concern and constant discussion. This aspect seems relevant and should be the subject of thorough discussion with the woman planning childbirth. Introduction: Current data concerning the impact of pregnancy and parity covers primarily retinopathy and nephropathy, while the aspects of neuropathy and macrovascular complications are unsatisfactorily documented. Majority of studies focus on single complication only, while the number of papers assessing this problem in a complex setting is limited. The available body of evidence concerns mainly the short-term impact of pregnancy on diabetic chronic complications while the data concerning the longer perspective are scarce. Moreover, the results found in the available literature are conflicting. The aim of the study was to summarize all available data concerning the longer impact of parity on the chronic complications in the women with type 1 diabetes. Methods: PubMed database has been searched between October 2013 and September 2018 and all relevant papers were selected. This review summarizes data on the impact of pregnancy and parity on chronic complications in type 1 diabetic women. Results: Current data assessing this matter in a complex way are limited, and the available results are controversial. It seems however that pregnancy itself may rather influence pre-existing diabetic complication than affect risk of its development. Additionally, evidence suggests that any deleterious changes appearing during pregnancy are transient and tend to remit after delivery. Conclusion: It seems that neither pregnancy nor parity affects the risk of diabetic chronic complications in the longer perspective.

There is ongoing debate surrounding the complex relationship between dietary sodium intake and cardiovascular morbidity and mortality. The existing literature consists largely of observational studies that have demonstrated positive, negative, U-/J-shaped or unclear associations between sodium intake and cardiovascular outcomes. Our group and others have previously demonstrated an inverse relationship between dietary sodium intake and cardiovascular outcomes in people with type 2 diabetes. Increased activity of the renin-angiotensin-aldosterone system and sympathetic nervous system is postulated to contribute to these paradoxical findings through endothelial dysfunction, a precursor to the development of cardiovascular disease. Microvesicles are submicron (0.1 – 1.0μm) vesicles that form during cellular activation, injury or death with endothelial microvesicles being recognized markers of endothelial dysfunction. They are pathologically elevated in a variety of vascular-related conditions including type 2 diabetes. Lower habitual sodium intake in type 2 diabetes has been associated with higher pro-coagulant platelet microvesicles levels but not with endothelial microvesicles. Research utilizing endothelial microvesicles to evaluate the mechanistic relationship between dietary sodium intake and adverse cardiovascular outcomes in type 2 diabetes remains scarce.

The prevalence of type 2 diabetes mellitus (T2DM) has quadrupled within three decades since 1980, affecting 422 million adults in 2016. It remains one of the most common noncommunicable chronic diseases and the underlying risk factor for cardiovascular diseases worldwide. There are different underlying mechanisms that play a role in the development of pathologies associated with the disease such as hyperglycaemia, oxidative stress, obesity, inflammation and hypercoagulation; each of which are interlinked. Hyperglycaemia, oxidative stress and obesity play a huge role in the activation of inflammation and coagulation. Activation of inflammatory pathways increases the production of thrombin which predisposes the development of thrombotic related diseases. One of the factors that contribute to the increase of thrombin is the impairment of the fibrinolysis process due to decreased expression of tissue-plasminogen activator (tPA) by increased levels of plasminogen activator inhibitor-1 (PAI-1). Coagulation factor XIII (FXIII), a transglutaminase that is composed of subunits A and B (FXIII-A2B2), is essential for the last step of fibrin clot formation in the coagulation pathway. Genetic variation of FXIII-A in the form of single nucleotide polymorphisms (SNPs) alters the activity of FXIII, altering clot properties which influence disease outcomes. This review discusses the link between underlying mechanisms of T2DM, well known FXIII-A variants and coagulation.

Background: Type 2 diabetes represents an increasing health burden world-wide and its prevalence in particularly higher in elderly population. Consistent epidemiological evidence suggests an increased risk of dementia associated to type 2 diabetes; the mechanisms underlying these associations, however, remain unclear. Objective: The study aims to review epidemiological, clinical and pre-clinical data that weigh on pathophysiological links, mechanisms of disease and associations between type 2 diabetes and dementia to identify areas of opportunity for future research. Methods: We searched the following electronic bibliographic databases: PUBMED, EMBASE, SCIELO, MEDLINE and OVID for clinical, translational and epidemiological research literature that summarize diabetes-related risk factors for dementia, metabolic and neurological changes associated to T2D, evidence of therapeutic approaches in type 2 diabetes and its pathophysiological implications for dementia. Results: Type 2 diabetes mellitus increases risk for all-cause dementia, vascular dementia and Alzheimer’s disease. The most evaluated mechanisms linking both disorders in pre-clinical studies include an increase in neuronal insulin resistance, impaired insulin signaling, pro-inflammatory state, mitochondrial dysfunction and vascular damage which increase deposition of β-amyloid, tau proteins and GSK3β, leading to an earlier onset of dementia in individuals with impairment in the glucose metabolism. Neuroimaging and neuropathology evidence linking cerebrovascular lesions, neurodegeneration and particularly small-vessel disease in the onset of dementia is consistent with the increased risk of incident dementia in type 2 diabetes, but consistent evidence of AD-related pathology is scarce. Epidemiological data shows increased risk of dementia related to hypoglycemic episodes, glycemic control, metabolic syndrome, insulin resistance and genetic predisposition, but the evidence is not consistent and statistical analysis might be affected by inconsistent covariate controlling. Therapeutic approaches for T2D have shown inconsistent result in relation to dementia prevention and delay of cognitive decline; lifestyle intervention, particularly physical activity, is a promising alternative to ameliorate the impact of disability and frailty on T2D-related dementia. Conclusion: Vascular disease, inflammation and impaired brain insulin signaling might occur in T2D and contribute to dementia risk. Evidence from epidemiological studies has not consistently reported associations that could integrate a unified mechanism of disease in humans. Evaluation of the effect of antidiabetic medications and non-pharmacological interventions in dementia prevention in type 2 diabetes is promising but has thus far offered inconsistent results.

Background: Diabetes Mellitus (DM) is a chronic life-long progressive multisystem heterogeneous metabolic disorder with complex pathogenesis. Introduction: Hyperglycemia is not only one of the classical signs of DM, but it also serves as the pivotal prerequisite for the diagnosis of the disease. However, with the advancement in the field of analytical biochemistry, a number of alternative and specific biomarkers have been discovered which can be used for better diagnosis of the DM. In this review, we have discussed various aspects of DM and different biomarkers used in assessing glycemia. Methodology: A thorough literature survey was conducted to identify various studies that reported the use of conventional and non-conventional markers for the assessment of glycemia in DM patients. Conclusion: The accurate detection and hence diagnosis of DM has become easy and more specific with the use of various biomarkers.

Background: Symbiotic interactions of microorganisms are widespread in nature, and support fundamentally important processes linking health and disease to the bacterial ecology. Intestinal microbiota is the largest source of microbial stimulation that exerts both harmful and beneficial effects on human health. It participates in the development of the postnatal immune system as well as oral tolerance and immunity. The recently explored impact of the microbiota on energy metabolism, gut hormone regulation and the gut-brain axis was judged to be a fascinating topic and of great value in the future, and can have a clinical role in the management of obesity and diabetes. Objective: To assess the impact of the gut microbe, Lactobacillus acidophilus, in patients with type 2 Diabetes Mellitus (controlled and uncontrolled) compared to healthy individuals, as a preliminary approach to future treatment with probiotics, prebiotics or diet modulation. Methods: A case control study was conducted on 30 diabetic patients and 10 control individuals. All patients were subjected to full history, thorough clinical examination, and laboratory measurement of fasting blood sugar, 2 hours post prandial, Glycosylated Hemoglobin (HbA1C), CRP (C-Reactive Protein), Lipid profile, and Identification of stool Lactobacillus acidophilus by PCR (polymerase chain reaction) technique. Results: Significantly lower Stool Lactobacillus acidophilus PCR count among diabetic patients when compared to healthy control individuals. Conclusion: Stool Lactobacillus acidophilus PCR count was lower among type 2 diabetic patients, which may show relationship of lactobacillus with type 2 diabetes mellitus. However, further studies are needed to determine correlation or causation of this relationship.

Introduction: In research elevated Blood Pressure (BP) has been demonstrated to be a risk for the development of nephropathy and chronic renal disease (CKD) Or Diabetic Kidney Disease (DKD) among diabetics. However, no study has find correlation for the spot urine protein (UPr) excretion with elevated BP, Pulse Pressure (PP) and mean arterial pressure MAP). This technique was invented in the current study. Methods: 10,270 were recruited for more than 12 years. Demographically, 43%, 38%, and 16% showed hypertension, nephropathy and chronic renal disease, respectively. UPr demonstrated significant correlations with systolic BP (SBP) and diastolic BP (DPB), MAP and PP (p < 0.0001 for all). SBP, DBP, PP and MAP, UPr were observed to be higher among the groups with nephroaphty and CKD/DKD with highly significant p-values (all p < 0.05). With logistic regression, odds ratio of hypertension (HTN) with nephropathy was observed to be 2.99 (95% CI 2.44 to 3.7; p < 0.0001); and odds ratio of HTN with CKD/DK was 7.1 (95% CI 4.3 to 11.84; p<0.0001), indicating that HTN significantly contributes to the development of nephropathy and CKD/DKD in diabetics. Results: Invented regression models for the excretion of UPr from the kidney with elevated SBP, DBP, MAP and PP were highly significant (p < 0.0001 for all); UPr = -138.6 + [1.347 SBP] ; UPr = -93.4 + [1.62 DBP] ; UPr = -149.5 + [1.922 × MAP] ; UPr = -41.23 +[1.541 PP]. Conclusion: Current study is the first one to introduce this technique. These invented new equations can be used by physicians to estimate protein excretion in urine at bedside and outpatients departments for monitoring proteinuria and CKD/DKD.

Aims/Hypothesis: Diabetic foot complications remain very prevalent in the US and worldwide, and a major risk for devastating amputations. We evaluated the impact of establishing a fully integrated and specialized Podiatry service into a large tertiary academic health system to implement structured and targeted preventative foot care on limb salvage rates. Methods: Cross-sectional cohorts’ data mining analysis was conducted of all encounters for diabetes and any foot complications between 2000-2005 and 2010-2015, preceding and after full implementation of podiatry service, respectively. The primary outcome was the change in major non-traumatic lower extremity amputations. Secondary outcomes included minor non-traumatic lower extremity amputations, other diabetic foot complications, limb salvage procedures as documented by procedural coding, and location (outpatient, inpatient, ED) of service rendered. Results: We analyzed 100 million patient encounters that met the above criteria. Compared with the initial cohort, integration of specialized podiatry services resulted in a significant decrease in the number of major amputations from 127 to 85/year (p<0.05), and halved the amputations rate from 0.004% to 0.002% (p<0.05). Rates of minor lower extremity amputations remained unchanged (p>0.10), while the rates of preventative procedures including foot ulcer debridement doubled (0.0002% to 0.0004% ; p<0.03). Diagnoses of diabetic foot complications increased significantly (p<0.05) and shifted toward the outpatient setting. Conclusion: Full integration of specialized Podiatry service led to a significant decrease in major amputation rates, supporting teamwork between podiatry and diabetes health-care providers is essential to performing timely diabetic foot complications management, preventative procedures leading to limb salvage, and a shift in the care location.

Background: Diabetes mellitus is a public health problem worldwide. The diabetic foot has a degenerate vascular structure, and its patients present neurological problems, which require the earliest possible identification. Introduction: The objective of the research was to use infrared thermography to analyze the temperature difference of the feet of users with diabetes mellitus with neuropathy, vasculopathy, neurovascular disease, or none of them, segmenting the sole of the foot in four areas for the study. Methods: A type of descriptive, cross-sectional and observational study was developed in a group of 277 patients with diabetic pathology (138 men and 139 women), with an average age of 63.41 ± 17.69 years and a body mass index of 29.08 ± 5.86, delimited in four groups: 22 (7.94%) with neuropathy, 32 (11.55%) with vasculopathy, 83 (29.96%) with neurovasculopathy and 140 (50.54%) without previous pathology. Thus, almost half of the sample (49.46%) presented some type of complication (neuropathic, vasculopathic or both). The photographic images were made with an infrared camera model FLIR E60bx®. The data obtained were analyzed using the IBM SPSS Statistics 22 statistical program. Results: There were lower temperatures under the 1st metatarsal head, the 5th metatarsal head, the heel, and pulp of the big toe of both left and right feet of the patients in the neuropathy, vasculopathy, and neurovasculopathy groups relative to the group with neither pathology. Conclusion: Infrared thermography can be useful in assessing the foot at risk to reveal the variability of temperature according to the study area, which may be useful for medical judgment and the predisposition to identify lesions in compromised regions of the foot.

Objective: The epidemic of T2DM is rising across the globe. Systemic inflammation plays a pivotal role in the pathogenesis and complications of T2DM. Combination of two or more oral hypoglycemic agents (OHA) is widely prescribed in patients with T2DM, however many patients have poor glycemic control despite receiving combination therapy. The new antidiabetic drugs are relatively costly or many patients have anxiety over the use of injectable insulin. The objective of this observational study was to investigate the effectiveness and tolerability of hydroxychloroquine (HCQ) in T2DM patients uncontrolled on multiple OHA and despite high sugar level not willing to initiate insulin therapy in a real-world clinical setting. Methods: A prospective, investigator-initiated, observational, single-centred study was conducted where 250 patients (18-65 years) with T2DM for more than 5 years, with uncontrolled glycemia despite on a combination of multiple OHA, HbA1c between ≥7% and <10.5%, FPG >130 mg/dL or PPG >180 mg/dL and BMI between >25 and <39 kg/m2, were prescribed hydroxychloroquine sulphate 400 mg once daily for 48 weeks. Percentage of drugs used at the baseline were as follows: metformin 2000 mg (100%), glimepiride 4 mg (100%), pioglitazone 30 mg (100%), sitagliptin 100 mg (100%), canagliflozin 300 mg (52.4%), empagliflozin 25 mg (22.8%), dapagliflozin 10 mg (17.6%) and voglibose 0.3 mg (62%). Mean change in HbA1c, blood glucose and hs-CRP at baseline, week 12, 24 and 48 were assessed using the paired t-test. Results: After 48 weeks of add-on treatment with HCQ, almost all SGLT-2 inhibitors were withdrawn; metformin dose was reduced to 1000 mg, glimepiride reduced to 1 mg and sitagliptin reduced to 50 mg OD. Patients continued to have good glycemic control. HbA1c was reduced from 8.83% to 6.44%. Reduction in FPG was 40.78% (baseline 177.30 mg/dL) and PPG was reduced by 58.95% (baseline 329.86 mg/dL). Change in mean body weight was -4.66 Kg. The reduction in glycemic parameters and mean body weight was significant (p < 0.0001). Hs-CRP was significantly reduced from 2.70±1.98 mg/L to 0.71±0.30 mg/L 9 (p < 0.0001). More reduction in glycemic parameters and body weight was observed among the patients with higher hs-CRP (> 3 mg/L) as compared to patients with baseline hs- CRP ≤ 3 mg/L. Most common adverse events reported with the drug therapy were GI irritation (3.6%) and hypoglycemia (2%). None of the patients required medical assistance for hypoglycemia. Conclusion: Add-on treatment of HCQ effectively improved glycemic control in T2DM patients uncontrolled on multiple antidiabetic drugs. By virtue of its antidiabetic and anti-inflammatory properties, it may emerge as a valuable therapeutic intervention for the patients with T2DM.