Female sex is a risk factor for painful diabetic peripheral neuropathy: the EURODIAB prospective diabetes complications study.

AIMS/HYPOTHESIS: While the risk factors for diabetic peripheral neuropathy (DPN) are now well recognised, the risk factors for painful DPN remain unknown. We performed analysis of the EURODIAB Prospective Complications Study data to elucidate the incidence and risk factors of painful DPN. METHODS: The EURODIAB Prospective Complications Study recruited 3250 participants with type 1 diabetes who were followed up for 7.3±0.6 (mean ± SD) years. To evaluate DPN, a standardised protocol was used, including clinical assessment, quantitative sensory testing and autonomic function tests. Painful DPN (defined as painful neuropathic symptoms in the legs in participants with confirmed DPN) was assessed at baseline and follow-up. RESULTS: At baseline, 234 (25.2%) out of 927 participants with DPN had painful DPN. At follow-up, incident DPN developed in 276 (23.5%) of 1172 participants. Of these, 41 (14.9%) had incident painful DPN. Most of the participants who developed incident painful DPN were female (73% vs 48% painless DPN p=0.003) and this remained significant after adjustment for duration of diabetes and HbA1c (OR 2.69 [95% CI 1.41, 6.23], p=0.004). The proportion of participants with macro- or microalbuminuria was lower in those with painful DPN compared with painless DPN (15% vs 34%, p=0.02), and this association remained after adjusting for HbA1c, diabetes duration and sex (p=0.03). CONCLUSIONS/INTERPRETATION: In this first prospective study to investigate the risk factors for painful DPN, we definitively demonstrate that female sex is a risk factor for painful DPN. Additionally, there is less evidence of diabetic nephropathy in incident painful, compared with painless, DPN. Thus, painful DPN is not driven by cardiometabolic factors traditionally associated with microvascular disease. Sex differences may therefore play an important role in the pathophysiology of neuropathic pain in diabetes. Future studies need to look at psychosocial, genetic and other factors in the development of painful DPN.

Genetic Variants Influence the Development of Diabetic Neuropathy.

The exact mechanism by which diabetic neuropathy develops is still not fully known, despite our advances in medical knowledge. Progressing neuropathy may occur with a persistently favorable metabolic status in some patients with diabetes mellitus, while, in others, though seldom, a persistently unfavorable metabolic status is not associated with significant neuropathy. This might be significantly due to genetic differences. While recent years have brought compelling progress in the understanding of the pathogenetic background-in particular, accelerated progress is being made in understanding molecular biological mechanisms-some aspects are still not fully understood. A comparatively small amount of information is accessible on this matter; therefore, by summarizing the available data, in this review, we aim to provide a clearer picture of the current state of knowledge, identify gaps in the previous studies, and possibly suggest directions for future studies. This could help in developing more personalized approaches to the prevention and treatment of diabetic neuropathy, while also taking into account individual genetic profiles.

Genetic Factors Associated with the Development of Neuropathy in Type 2 Diabetes.

Neuropathy is a serious and frequent complication of type 2 diabetes (T2DM). This study was carried out to search for genetic factors associated with the development of diabetic neuropathy by whole exome sequencing. For this study, 24 patients with long-term type 2 diabetes with neuropathy and 24 without underwent detailed neurological assessment and whole exome sequencing. Cardiovascular autonomic function was evaluated by cardiovascular reflex tests. Heart rate variability was measured by the triangle index. Sensory nerve function was estimated by Neurometer and Medoc devices. Neuropathic symptoms were characterized by the neuropathy total symptom score (NTSS). Whole exome sequencing (WES) was performed on a Thermo Ion GeneStudio S5 system determining the coding sequences of approximately 32,000 genes comprising 50 million base pairs. Variants were detected by Ion Reporter software and annotated using ANNOVAR, integrating database information from dbSNP, ClinVar, gnomAD, and OMIM. Integrative genomics viewer (IGV) was used for visualization of the mapped reads. We have identified genetic variants that were significantly associated with increased (22-49-fold) risk of neuropathy (rs2032930 and rs2032931 of recQ-mediated genome instability protein 2 (RMI2) gene), rs604349 of myosin binding protein H like (MYBPHL) gene and with reduced (0.07-0.08-fold) risk (rs917778 of multivesicular body subunit 12B (MVB12B) and rs2234753 of retinoic acid X receptor alpha (RXRA) genes). The rs2032930 showed a significant correlation with current perception thresholds measured at 5 Hz and 250 Hz for n. medianus (p = 0.042 and p = 0.003, respectively) and at 5 Hz for n. peroneus (p = 0.037), as well as the deep breath test (p = 0.022) and the NTSS (p = 0.023). The rs2032931 was associated with current perception thresholds (p = 0.003 and p = 0.037, respectively), deep breath test (p = 0.022), and NTSS (p = 0.023). The rs604349 correlated with values measured at 2000 (p = 0.049), 250 (p = 0.018), and 5 Hz (p = 0.005) for n. medianus, as well as warm perception threshold measured by Medoc device (p = 0.042). The rs2234753 showed correlations with a current perception threshold measured at 2000 Hz for n. medianus (p = 0.020), deep breath test (p = 0.040), and NTSS (p = 0.003). There was a significant relationship between rs91778 and cold perception threshold (p = 0.013). In our study, genetic variants have been identified that may have an impact on the risk of neuropathy developing in type 2 diabetic patients. These results could open up new opportunities for early preventive measures and might provide targets for new drug developments in the future.

The Relationship between COVID-19 and Hypothalamic-Pituitary-Adrenal Axis: A Large Spectrum from Glucocorticoid Insufficiency to Excess-The CAPISCO International Expert Panel.

Coronavirus disease 2019 (COVID-19) is a highly heterogeneous disease regarding severity, vulnerability to infection due to comorbidities, and treatment approaches. The hypothalamic-pituitary-adrenal (HPA) axis has been identified as one of the most critical endocrine targets of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that might significantly impact outcomes after infection. Herein we review the rationale for glucocorticoid use in the setting of COVID-19 and emphasize the need to have a low index of suspicion for glucocorticoid-induced adrenal insufficiency, adjusting for the glucocorticoid formulation used, dose, treatment duration, and underlying health problems. We also address several additional mechanisms that may cause HPA axis dysfunction, including critical illness-related corticosteroid insufficiency, the direct cytopathic impacts of SARS-CoV-2 infection on the adrenals, pituitary, and hypothalamus, immune-mediated inflammations, small vessel vasculitis, microthrombotic events, the resistance of cortisol receptors, and impaired post-receptor signaling, as well as the dissociation of ACTH and cortisol regulation. We also discuss the increased risk of infection and more severe illness in COVID-19 patients with pre-existing disorders of the HPA axis, from insufficiency to excess. These insights into the complex regulation of the HPA axis reveal how well the body performs in its adaptive survival mechanism during a severe infection, such as SARS-CoV-2, and how many parameters might disbalance the outcomes of this adaptation.

Changing Patterns of Antihyperglycaemic Treatment among Patients with Type 2 Diabetes in Hungary between 2015 and 2020-Nationwide Data from a Register-Based Analysis.

Background and objectives: In the last couple of years, pharmacological management of patients with type 2 diabetes mellitus (T2DM) have been markedly renewed. The aim of this study was to analyse the changes in prescribing patterns of antidiabetic drugs for treating patients with T2DM in Hungary between 2015 and 2020. Material and Methods: In this retrospective, nationwide analysis, we used the central database of the National Health Insurance Fund. We present annual numbers and their proportion of T2DM patients with different treatment regimens. Results: In the period of 2015−2020, the number of incident cases decreased from 60,049 to 29,865, while prevalent cases increased from 682,274 to 752,367. Patients with metformin (MET) monotherapy had the highest prevalence (31% in 2020). Prevalence of insulin (INS) monotherapy continuously but slightly decreased from 29% to 27% while that of sulfonylurea (SU) monotherapy markedly decreased from 37% to 20%. Dipeptidyl peptidase (DPP-4) inhibitors remained popular in 2020 as monotherapy (5%), in dual combination with MET (12%) and in triple combination with MET and SU (5%). The prevalence of patients with sodium-glucose co-transporter-2 (SGLT-2) inhibitors increased from 1% to 4% in monotherapy, from <1% to 6% in dual combination with MET, and from <1% to 2% in triple oral combination with MET and SU or DPP-4-inhibitors. The prevalence of patients using glucagon-like peptide-1 receptor agonists (GLP-1-RAs) also increased but remained around 1−2% both in monotherapy and combinations. For initiating antihyperglycaemic treatment, MET monotherapy was the most frequently used regime in 2020 (50%), followed by monotherapy with SUs (16%) or INS (10%). After initial MET monotherapy, the incidence rates of patients with add-on GLP-1-RAs (2%, 3%, and 4%) and those of add-on SGLT-2 inhibitors (4%, 6%, and 8%) slowly increased in the subsequent 24, 48, and 72 months, respectively. Conclusions: In the period of 2015−2020, we documented important changes in trends of antihyperglycaemic therapeutic patterns in patients with T2DM which followed the new scientific recommendations but remained below our expectations regarding timing and magnitude. More efforts are warranted to implement new agents with cardiovascular/renal benefits into therapeutic management in time, in a much larger proportion of T2DM population, and without delay.

Worldwide inertia to the use of cardiorenal protective glucose-lowering drugs (SGLT2i and GLP-1 RA) in high-risk patients with type 2 diabetes.

The disclosure of proven cardiorenal benefits with certain antidiabetic agents was supposed to herald a new era in the management of type 2 diabetes (T2D), especially for the many patients with T2D who are at high risk for cardiovascular and renal events. However, as the evidence in favour of various sodium-glucose transporter-2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) accumulates, prescriptions of these agents continue to stagnate, even among eligible, at-risk patients. By contrast, dipeptidyl peptidase-4 inhibitors (DPP-4i) DPP-4i remain more widely used than SGLT2i and GLP-1 RA in these patients, despite a similar cost to SGLT2i and a large body of evidence showing no clear benefit on cardiorenal outcomes. We are a group of diabetologists united by a shared concern that clinical inertia is preventing these patients from receiving life-saving treatments, as well as placing them at greater risk of hospitalisation for heart failure and progression of renal disease. We propose a manifesto for change, in order to increase uptake of SGLT2i and GLP-1 RA in appropriate patients as a matter of urgency, especially those who could be readily switched from an agent without proven cardiorenal benefit. Central to our manifesto is a shift from linear treatment algorithms based on HbA1c target setting to parallel, independent considerations of atherosclerotic cardiovascular disease, heart failure and renal risks, in accordance with newly updated guidelines. Finally, we call upon all colleagues to play their part in implementing our manifesto at a local level, ensuring that patients do not pay a heavy price for continued clinical inertia in T2D.

Young adult patients with type 1 diabetes have a higher risk of mortality than those of similar age with type 2 diabetes: A nationwide analysis in Hungary.

BACKGROUND: There are few papers comparing complications of type 1 diabetes with those of a similarly young age with type 2 diabetes. The aim of our nationwide study was to compare the risks of mortality and morbidities between the two types of diabetes (age ≤ 40). METHODS: We identified all young adult patients with type 1 diabetes who were recorded in the database of the Hungarian National Health Insurance Fund between 2001 and 2014 (n = 11 863) and compared them with a population of similar age with young adult type 2 diabetes (n = 47 931). The incidence of all-cause mortality, myocardial infarction, stroke, any type of cancer, diabetic ketoacidosis, and hypoglycemia was followed from the onset of diabetes to the date of death or end of study period. RESULTS: The risks of all-cause mortality were significantly higher in patients with type 1 compared with patients with type 2 diabetes (hazard ratio, 95%CI; 2.17, 1.95-2.41; P < .0001). The risks of myocardial infarction (0.90, 0.71-1.13; P = 0.36) and stroke (1.06, 0.87-1.29; P = .582) were not significantly different in type 1 compared with type 2. In contrast, the risk of cancer (1.35, 1.15-1.59; P = .0003), dialysis (2.20, 1.76-2.75; P < .0001), hypoglycemia (7.70, 6.45-9.18; P < .0001), and ketoacidosis (22.12, 19.60-25.00; P < .0001) was higher among patients with type 1 compared with those with type 2 diabetes. CONCLUSIONS: A comparatively higher incidence of diabetic ketoacidosis and hypoglycemia and higher risk of cancer and dialysis in patients with type 1 diabetes than in those with type 2 may play a role in the higher risk of mortality.

Dissimilar impact of type 2 diabetes on cardiovascular outcomes according to age categories: a nationwide population study from Hungary.

BACKGROUND: The excess risks of mortality and cardiovascular morbidity among patients with type 2 diabetes mellitus (T2DM) is well known. In this nationwide study, we assessed risks of mortality and cardiovascular events comparing patients with T2DM and matched controls. METHODS: We identified patients with T2DM in a retrospective cohort study using the database of the National Health Insurance Fund between 1 January 2010 and 31 December, 2013. Controls were randomly included and matched according to age, gender, and zip code of residence. Patients were divided into subgroups according to age decades for outcome analyses. RESULTS: During the mean follow-up period of 2.3 years, 152,678 patients with T2DM and 305,356 matched controls were included. Patients with T2DM showed significantly higher risk for all-cause mortality (HR 1.26, 95% CI 1.22-1.29, p < 0.0001), myocardial infarction (HR 1.81, 95% CI 1.69-1.94, p < 0.0001) and stroke (HR 1.40, 95% CI 1.35-1.46, p < 0.0001) compared to matched controls. The higher risk associated with T2DM for mortality, myocardial infarction and stroke differed significantly between age groups (pinteraction < 0.05 for all outcomes) with significantly higher risk observed in younger patients. CONCLUSIONS: The risk of cardiovascular outcomes and all-cause mortality is significantly higher in patients with T2DM. Notably, the relative hazard increases with decreasing age suggesting that younger patients with T2DM should receive more attention for cardiovascular prevention.

Translating recent results from the Cardiovascular Outcomes Trials into clinical practice: recommendations from the Central and Eastern European Diabetes Expert Group (CEEDEG).

AIMS: These recommendations aim to improve care for patients with type 2 diabetes (T2D) at high cardiovascular (CV) risk in Central and Eastern Europe. Cardiovascular disease (CVD) and/or chronic kidney disease (CKD) are major interdependent comorbidities in patients with T2D, accounting for 50% of mortality. Following recent CV outcomes trial (CVOT) results, including those from EMPA-REG OUTCOME®, LEADER®, SUSTAIN™-6 and, most recently, the CANVAS study, it is essential to develop regional expert consensus recommendations to aid physicians in interpreting these newest data to clinical practice. METHODS: The Central and Eastern European Diabetes Expert Group (CEEDEG) followed a Delphi method to develop treatment algorithms to aid physicians in the clinical management of patients with T2D at high CV risk. RESULTS: In light of the latest CVOT results, and in particular the EMPA-REG OUTCOME® and LEADER® trials, the diagnosis, assessment, treatment choice and monitoring of patients with T2D and established CVD and/or CKD have been considered together with existing guidelines and presented in two reference algorithms. In addition, adherence, special prescribing considerations and a proposed multidisciplinary management approach have been discussed and are presented with the proposed algorithms. CONCLUSIONS: The latest available high-level evidence on glucose-lowering drugs has enabled CEEDEG to develop practical consensus recommendations for patients with established CVD and/or CKD. These recommendations represent an update to international and country-level guidelines used for these patients, with the aim of providing a resource not only to endocrinologists, but to cardiologists, nephrologists and primary care physicians in the region.

[Trends in antidiabetic treatment prescribed for patients with type 2 diabetes in Hungary between 2001 and 2014 - results from the database analysis of the National Health Insurance Fund]. / A 2-es típusú diabetes antihyperglykaemiás kezelésének alakulása Magyarországon 2001­2014 között ­ az Országos Egészségbiztosítási Pénztár adatbázis-elemzésének eredményei.

In the last couple of years, significant developments in antidiabetic treatment have influenced the pharmacological treatment of type 2 diabetes mellitus (T2DM). The aim of this study was to analyze the changes in prescribing patterns of glucose-lowering drugs for T2DM patients in Hungary between 2001 and 2014. The number of patients with newly diagnosed T2DM decreased from 75,700 (2001) to 33,700 (2014), while prevalent T2DM cases continuously increased and plateaued in 2014 with a number of registered patients of 727,000. Sulfonylurea-monotherapy decreased from 64% to 35% while metformin-monotherapy increased from 19% to 42% in this period. The most frequently used drug at first treatment initiation was metformin (66%) and sulfonylurea (16%) as monotherapy in 2014. DPP4-inhibitors were newly administered in 20,362 cases while GLP1-mimetics were newly used by 4,996 patients in 2014. Five years later after initiating sulfonylurea therapy between 2010 and 2014, metformin was more frequently used as second drug (39%) than sulfonylurea in patients with previous metformin treatment (22.9%). The prescribing patterns of glucose-lowering drugs have changed over time in accordance with new guidelines. Further changes in prescribing habits can be expected in the near future. Orv Hetil. 2017; 158(20): 770-778.

[Changes in features of diabetes care in Hungary in the period of years 2001-2014. Aims and methods of the database analysis of the National Health Insurance Fund]. / A cukorbeteg-ellátás mutatóinak alakulása Magyarországon 2001-2014 között. Az Országos Egészségbiztosítási Pénztár adatbázis-elemzésének célja és módszertana.

In the last couple of years, database analyses have become increasingly popular among clinical-epidemiological investigations. In Hungary, the National Health Insurance Fund serves as central database of all medical attendances in state departments and purchases of drug prescriptions in pharmacies. Data from in- and outpatient departments as well as those from pharmacies are regularly collected in this database which is public and accessible on request. The aim of this retrospective study was to investigate the database of the National Health Insurance Fund in order to analyze the diabetes-associated morbidity and mortality in the period of years 2001-2014. Moreover, data of therapeutic costs, features of hospitalizations and practice of antidiabetic treatment were examined. The authors report now on the method of the database analysis. It is to be hoped that the upcoming results of this investigation will add some new data to recent knowledge about diabetes care in Hungary. Orv. Hetil., 2016, 157(32), 1259-1265.

Diabetes-related dysfunction of the small intestine and the colon: focus on motility.

In contrast to gastric dysfunction, diabetes-related functional impairments of the small and large intestine have been studied less intensively. The gastrointestinal tract accomplishes several functions, such as mixing and propulsion of luminal content, absorption and secretion of ions, water, and nutrients, defense against pathogens, and elimination of waste products. Diverse functions of the gut are regulated by complex interactions among its functional elements, including gut microbiota. The network-forming tissues, the enteric nervous system) and the interstitial cells of Cajal, are definitely impaired in diabetic patients, and their loss of function is closely related to the symptoms in diabetes, but changes of other elements could also play a role in the development of diabetes mellitus-related motility disorders. The development of our understanding over the recent years of the diabetes-induced dysfunctions in the small and large intestine are reviewed in this article.

Heart rate variability is severely impaired among type 2 diabetic patients with hypertension.

INTRODUCTION: The aim of our study was to evaluate the relative effect of diabetes and hypertension on heart rate variability. RESEARCH DESIGN AND METHODS: Four age-matched groups including type 2 diabetic patients with and without hypertension, non-diabetic patients with essential hypertension and healthy control subjects were studied. Autonomic function was evaluated by the standard cardiovascular reflex tests and 24-hour heart rate variability measurement. Heart rate variability was characterized by the triangular index value and by the spectral components of the frequency domain analysis. RESULTS: According to the two-way analysis of variance on ranks, all parameters were influenced negatively by diabetes (heart rate variability triangular index: p < 0.001; low-frequency component: p < 0.0001; high-frequency component: p < 0.001; and total power: p < 0.0001), whereas hypertension had a negative effect only on the low-frequency component (p < 0.05). The interaction between hypertension and diabetes was not significant, indicating that their effects on the heart rate variability parameters are additive. Beat-to-beat variation upon deep breathing, the most sensitive cardiovascular reflex test was also negatively influenced by both diabetes (p < 0.001) and hypertension, (p < 0.05), and their effects were additive. CONCLUSIONS: Diabetes appears to have a greater effect on autonomic dysfunction compared with hypertension. Patients suffering from both diabetes and hypertension are at the highest risk of reduced heart rate variability. Early assessment of the autonomic nerve function is suggested in diabetic patients with hypertension.

Diabetic gastroparesis: functional/morphologic background, diagnosis, and treatment options.

The regulation of gastrointestinal motility mainly involves the smooth muscle, neural (extrinsic and intrinsic), and hormonal elements, the glial cells, and the interstitial cells of Cajal. An orchestrated function of all these components is required for the appropriate propulsive movement of the food in the gastrointestinal tract. Gastroparesis, a pathological slowing-down of gastric emptying, is a result of the damage to the tissue elements involved in the regulation of motility. Gastroparesis is one of the well-known complications of long-standing diabetes mellitus. Although it is rarely a life-threatening complication, it has a deteriorating effect on the quality of life, leads to unpredictable oscillation of the blood glucose level, and increases the time required for the absorption of food and medicines. This review describes the clinical characteristics of diabetic gastroparesis and summarizes the organic and functional motility abnormalities caused by this complication. Finally, the currently available and potential future therapeutic approaches are summarized.

Is there an association between diabetic neuropathy and low vitamin D levels?

In the past few years, the effects of vitamin D that go beyond its relationship with bone metabolism have come into the focus of scientific attention. Research concerning diabetes and its complications has become a public health priority. An increasing number of reports link vitamin D deficiency to diabetes; however, so far, there has only been limited and contradictory data available on the correlation between diabetic peripheral neuropathy and vitamin D. Studies of people with type 2 diabetes confirmed the relationship between vitamin D deficiency and neuropathy incidence as well as the severity of the symptoms caused by neuropathy. The latest studies are also suggesting a relationship between the incidence of plantar ulcers and vitamin D deficiency.

No clear evidence of neuropathy among patients with high risk for the development of prediabetes/diabetes-a pilot study.

Introduction: Autonomic and sensory neuropathy have been observed in both prediabetes and manifest diabetes mellitus. However, there is a lack of available data regarding whether patients at a moderate or high risk of developing diabetes, yet without a current diagnosis of prediabetes or diabetes, exhibit an increased prevalence of neuropathy. Methods: FINDRISC (Finnish Diabetes Risk Score) was used to classify individuals at risk (≥12 points, n = 44; control <12 points, n = 28). HbA1c levels >5.6% served as exclusion criteria, and patients with known medical conditions predisposing to neuropathy were also excluded. Cardiac autonomic function (Ewing tests) and peripheral sensory neuropathy (Neurometer and Q-sense) were assessed by standardized protocols, and their potential association with increased FINDRISC points was analyzed using a regression model. Results: Mean age was 46.7 ± 14.3 years in the control and 55.7 ± 14.1 years in the increased risk group. Male/female ratio did not differ. Individuals with increased risk of diabetes were more obese (BMI: 29.9 ± 12.5 kg/m2 vs. 25.9 ± 8.9 kg/m2). Additionally, hypertension was more frequent among them (68.2% vs. 17.9%), and their lipid parameters were also less favorable. Parasympathetic neuropathy was present in both groups (56.8% vs. 32.1%, respectively). Sympathetic neuropathy was not found. Sensory nerve dysfunction was of low prevalence in the high-risk group and did not occur in healthy controls. In multiple logistic regression analysis, HbA1c exhibited an independent association with parasympathetic neuropathy (OR: 5.9; 95% CI: 1.08-32.68; p < 0.041). Discussion: An increased risk of developing prediabetes/diabetes does not appear to have a strong correlation with an increased likelihood of developing autonomic or sensory neuropathy. However, the etiology behind the occurrence of parasympathetic autonomic neuropathy in healthy individuals remains unknown.

Correlations between distal sensorimotor polyneuropathy and cardiovascular complications in diabetic patients in the North-Eastern region of Hungary.

Distal sensorimotor polyneuropathy (DSPN) is the earliest detectable and the most frequent microvascular complication in diabetes mellitus. Several studies have previously demonstrated correlations between cardiovascular risk factors in diabetic patients and independent risk factors for diabetic neuropathy. Our objective was to retrospectively analyze data from diabetic patients in the North-East region of Hungary who underwent neuropathy screening at the Diabetic Neuropathy Center, University of Debrecen, between 2017 and 2021. We aimed to investigate the correlations between cardiovascular risk factors and microvascular complications among patients with DSPN. The median age of the patients was 67 years, 59,6% were female, and 91,1% had type 2 diabetes. The prevalence of DSPN among the study subjects was 71.7%. A significantly longer duration of diabetes (p<0.01) was noted in patients with DSPN. Those with DSPN demonstrated a significantly higher HbA1c level (p<0.001) and a greater frequency of insulin use (p = 0.001). We observed a significantly elevated albumin/creatinine ratio (p<0.001) and a significantly lower eGFR (p<0.001) in patients with DSPN. Diabetic retinopathy exhibited a significantly higher prevalence in patients with DSPN (p<0.001). A higher prevalence of myocardial infarction (p<0.05), ischemic heart disease (p<0.001), peripheral arterial disease (p<0.05) and a history of atherosclerosis (p<0.05) was observed in patients with DSPN. In a multivariate logistic regression analysis, the following factors were independently associated with the presence of DSPN: higher HbA1c (OR:2.58, 95% CI:1.89-3.52, p<0.001), age (OR:1.03, 95% CI:1.01-1.05, p = 0.006), albumin/creatinine ratio above 3 mg/mmol (OR:1.23, 95% CI:1.06-1.45, p = 0.008), retinopathy (OR:6.06, 95% CI:1.33-27.53, p = 0.02), and composite cardiovascular endpoint (OR:1.95, 95% CI:1.19-3.19, p = 0.008). Our study revealed that age, elevated HbA1c levels, significant albuminuria, retinopathy, and cardiovascular complications may increase the risk of DSPN. Further investigation of these associations is necessary to understand the impact of patient characteristics during the treatment of diabetic neuropathy.

A comprehensive analysis of diabetic patient data before and during the COVID-19 pandemic - Lessons from the MÉRY diabetes database (MDD).

AIMS: Our study examined changes in average blood glucose levels (ABG), measurement frequency (MF), and data uploading (DU) before and during the COVID-19 pandemic in 882-day spans, which were divided into further 20-week intervals to highlight the pandemic's impact. METHODS: T-Tests assessed the statistical significance of blood glucose data from 26,655/20,936 patients and 19.5/16.6 million records during pre-COVID/COVID. RESULTS: During COVID, patients had significantly lower ABG levels (9.1/8.9 mmol/L, p < 0.001). Weekly DU decreased (155,945/128,445, p < 0.05), while daily MF increased (0.83/0.87, p < 0.001). Comparing the last 20 weeks pre-COVID to the first 20 weeks during COVID, ABG levels were lower (9.0 /8.9, p < 0.01), MF increased (0.83 /0.99, p < 0.001), and DU decreased (153,133/145,381, p < 0.05). In the initial 20 weeks of COVID compared to the second 20 weeks of COVID, ABG increased (8.9/9.1, p < 0.01), MF decreased (0.99/0.95, p < 0.001), and DU decreased (145,381/140,166, p < 0.05). Our most striking observation was the temporary dramatic fall in glucose uploads during the first few weeks of COVID. The changes of ABG and MF values were statistically significant, but were not deemed clinically relevant. CONCLUSIONS: Despite COVID's prolonged impact, diabetic patients showed improved attitudes. A significant drop in data uploads occurred during the first 20 weeks of COVID; home office and lockdowns apparently disrupted patient routines.

The handgrip test - A historical test for diabetic autonomic neuropathy or a marker of something else?

Cardiovascular autonomic neuropathy (CAN) is a frequent complication of diabetes mellitus and is associated with increased morbidity and mortality in patients with diabetes. Hence, early and correct diagnosis of CAN is crucial. Standard cardiovascular reflex rests (CARTs) have been the gold standard of CAN assessment. Originally, CARTs consisted of five reflex tests, but measuring diastolic blood pressure response to sustained handgrip exercise has no longer been suggested as an established clinical test. Increasing body of evidence suggests that isometric handgrip test should no longer be used for the evaluation of sympathetic dysfunction during cardiovascular autonomic neuropathy assessment in diabetic patients. The associations of isometric handgrip test results with parameters of hypertension and markers of hypertension-related target-organ damage in diabetic and non-diabetic individuals point toward its potential role as a screening tool to identify patients with high cardiovascular risk. The current review summarizes historical view of standard cardiovascular reflex tests and latest data on isometric handgrip test.