Autonomic Neuropathy Research Articles

The cumulative impact of type 2 diabetes and obstructive sleep apnoea on cardiovascular, liver, diabetes-related and cancer outcomes.

A bidirectional relationship exists between obstructive sleep apnoea (OSA) and type 2 diabetes (T2D). We aimed to examine the cumulative impact of having both OSA and T2D on patient outcomes, relative to having either condition alone. Using TriNetX, a global federated research network (n = 128 million), we undertook two retrospective cohort studies, using time-to-event analysis. Analysis 1 compared OSA with T2D versus OSA alone; analysis 2 compared T2D with OSA versus T2D alone. Propensity score matching using greedy nearest neighbour (calliper 0.1) balanced the cohorts (1:1) for significant covariates. Primary outcomes were cardiovascular, liver, diabetes-related (microvascular) and cancer events over 1-5 years. Analysis 1 (n = 179 688): A codiagnosis of T2D/OSA significantly increased risk of all-cause mortality (hazard ratio [HR] 1.52; confidence interval [CI]: 1.48, 1.57), dementia (HR 1.19; CI: 1.12, 1.26), liver (HR 2.20; CI: 1.77, 2.73), pancreatic (HR 1.62; CI: 1.35, 1.93), colon, renal and endometrial cancers; all cardiovascular, microvascular and liver related outcomes versus OSA alone over 1-5 5 years following OSA diagnosis. Analysis 2 (n = 240 094): A codiagnosis of OSA/T2D significantly increased the risk of peripheral (HR 1.39; CI: 1.36, 1.43) and autonomic (HR 1.63; CI: 1.51, 1.75) neuropathy; retinopathy (HR 1.13; CI: 1.09, 1.18), CKD (HR 1.21; CI: 1.18, 1.23); all cardiovascular and liver outcomes; all-cause mortality and several obesity related cancers versus T2D alone. T2D significantly potentiates risk of cardiovascular, malignancy and liver-related outcomes in individuals with OSA. OSA, in individuals with T2D, significantly potentiates risk of cardiovascular disease, malignancy, death and several microvascular complications (retinopathy, CKD, peripheral/autonomic neuropathy).

Systemic Amyloid Light Chain Amyloidosis With Repeated Syncope Due to Severe Orthostatic Hypotension Caused by Autonomic Neuropathy: A Case Report

Systemic Amyloid Light Chain Amyloidosis With Repeated Syncope Due to Severe Orthostatic Hypotension Caused by Autonomic Neuropathy: A Case Report

Prevalence of self-reported symptoms of diabetic autonomic dysfunction in the North Denmark Region: a population-based survey.

Diabetic autonomic neuropathy is a severe complication of diabetes, estimated to affect up to 44% in type 1 diabetes (T1D) and 73% in type 2 diabetes (T2D) based on clinical studies. Currently, the assessment of diabetic autonomic neuropathy is not implemented in Denmark's clinical guidelines, complicating the estimation of the true prevalence. Thus, this study investigated the prevalence of self-reported symptoms of autonomic dysfunction in people living with diabetes in the North Denmark Region using the Composite Autonomic Symptoms Score (COMPASS)-31 questionnaire. In 2022, all adults with T1D or T2D in the North Denmark Region (n = 29,155) were identified using The National Health Insurance Service Registry and invited to an online survey including the Danish version of COMPASS-31. The prevalence and associated 95% confidence intervals (CI) for symptomatic autonomic dysfunction were determined using a cut-off value of 16. In total, 7,377 completed COMPASS-31, of which 82.4% reported having T2D and 13.7% T1D. The prevalence of symptomatic autonomic dysfunction was 36.8% (95% CI: 34-40) after a median of 26 years with diabetes for T1D and 44.2% (95% CI: 43-45) after a median of 10 years for T2D. Pupillary and orthostatic intolerance were the most frequent moderate to severe symptoms, respectively (38.4% and 24.0% in T1D and 32.8% and 26.3% in T2D). Symptoms of autonomic dysfunction are very common in individuals with diabetes living in the North Denmark Region, emphasizing the unmet need for regular testing to increase awareness and allow for adequate management, ultimately reducing the morbidity of diabetes.

Autonomic and Immune Stress Response Networks in Patients Living With HIV.

Stress response systems are frequently dysregulated in patients with chronic inflammatory disorders. Pre-clinical studies have demonstrated direct influences of the sympathetic and vagal/parasympathetic branches of the autonomic nervous system (ANS) on the immune system. However, these connections have not been examined in humans. We hypothesized that the subtype and severity of autonomic neuropathy (AN) would predict immune phenotypes with distinct clinical and demographic characteristics in people living with HIV. This is a cross-sectional study of 79 adult people with a history of well-controlled HIV on stable combination antiretroviral treatment (CART) recruited from a primary care clinic network within the Mount Sinai Health System in New York City. All participants underwent a standardized battery of autonomic function tests summarized as the Composite Autonomic Severity Score (CASS) and vagal and adrenergic baroreflex sensitivity (BRS-V and BRS-A). Immune profiling included: 1) measurement of interleukin-6 (IL-6) as part of the Olink assay Target 96 Inflammation Panel, 2) non-negative matrix factorization (NMF) clustering analyses on Olink immune biomarkers, and 3) mass cytometry (CyTOF) on a subset of participants with and without autonomic neuropathy (N = 10). Reduced activity of caudal vagal circuitry involved in the cholinergic anti-inflammatory pathway (CAP) predicted higher levels of IL-6 (Spearman's rho = -0.352, p=0.002). The comprehensive assessment of the ANS-immune network showed four immunotypes defined by NMF analyses. A pro-inflammatory immunotype defined by elevations in type 1 cytokines (IL-6, IL-17) and increased numbers of CD8+ T-cells was associated with autonomic neuropathy (AN). This association was driven by deficits in the cardiovascular sympathetic nervous system and remained strongly significant after controlling for the older age and greater burden of co-morbid illness among participants with this immunotype (aOR=4.7, p=0.017). Our results provide novel support for the clinical relevance of the CAP in patients with chronic inflammatory AN. These data also provide insight regarding the role of the sympathetic nervous system and aging in the progression and development of co-morbidities in patients with chronic HIV and support future research aimed at developing therapies focused on modulation of the sympathetic and parasympathetic/vagal nervous system.

A Study on QTc Prolongation as an Indicator of Cardiac Autonomic Neuropathy in Diabetic Patients at Bir Hospital, Nepal

Background: Diabetes mellitus frequently leads to cardiac autonomic neuropathy (CAN), a complication that disrupts heart rate control and vascular function, increasing the risk of silent myocardial ischemia and sudden cardiac death. Prolonged QTc interval on ECG has emerged as a reliable marker for detecting CAN.  Objective: To study the QTc prolongation in diabetes mellitus as an indicator of cardiac autonomic neuropathy.  Methodology: A cross-sectional study was conducted on 100 diabetic patients at NAMS, Bir Hospital, Nepal, from September 2021 to June 2022. Data on QTc intervals and other clinical parameters were analyzed using STATA 13.0 software.  Results: Among the 100 patients, 60% were diagnosed with CAN. Of these, 20% had severe CAN and 40% had early-stage CAN. Patients with severe CAN had a longer duration of diabetes and higher blood sugar levels compared to those without CAN. QTc interval was significantly prolonged in 58% of patients with CAN, indicating a strong correlation between QTc prolongation and CAN severity.  Conclusion: QTc interval prolongation is closely associated with the severity of CAN, making it a practical and efficient tool for early detection in diabetic patients. Recognizing prolonged QTc can help identify patients at higher risk of sudden cardiac death, emphasizing the need for further large-scale studies.

Clinical Cues for the Early Diagnosis of Transthyretin-Related Polyneuropathy.

The estimated prevalence of hereditary transthyretin-related familial amyloid polyneuropathy (TTR-FAP) and the small number of known patients in Germany indicate that many patients with TTR-FAP remain undiagnosed, and may instead be classified as "idiopathic." The aim of this study was to identify biomarkers for detecting TTR-FAP among a cohort of patients with idiopathic polyneuropathy (PNP). Clinical evaluations (including the Neuropathy Impairment Score and Neuropathy Disability Score), nerve conduction studies (NCSs), quantitative sensory testing, and autonomic function tests were performed on 23 patients with TTR-FAP and 89 with idiopathic PNP. Discriminant analysis was then performed to identify variables useful for predicting TTR-FAP. Patients with TTR-FAP had paresis of the finger and thumb muscles, and reduced vibration perception and increased pressure pain in the upper and lower extremities. The NCSs showed that action potentials were smaller in the median, ulnar (both motor and sensory), and sural nerves in TTR-FAP. The sensory nerve conduction velocity was also reduced in the ulnar nerve. Autonomic neuropathy was confirmed by reduced sympathetic skin responses in the hands and feet in TTR-FAP. Multivariate discriminant analysis revealed that finger abduction strength, sensory ulnar nerve action potential amplitude, and vibration detection and pressure pain thresholds in the upper extremities were sufficient to correctly identify TTR-FAP in 81.3% of cases. Detailed clinical and neurophysiological investigations of standard parameters in the upper limb may help to identify the otherwise-rare TTR-FAP.

Spectrum of hereditary transthyretin amyloidosis due to T60A(p.Thr80Ala) variant in an Irish Amyloidosis Network

BackgroundVariant transthyretin amyloidosis (ATTRv) is a hereditary multisystem disorder with clinical spectrum ranging from predominant cardiomyopathy to polyneuropathy. In the Irish population, the T60A mutation has been previously recognised as...

Duration of diabetes, glycemic control, and low heart rate variability: The atherosclerosis risk in communities (ARIC) study

Persons with long-standing, poorly controlled diabetes or recent hyperglycemia had the highest burden of cardiac autonomic neuropathy. Cardiac autonomic neuropathy contributed to elevated long-term incidence of cardiovascular disease and mortality even in persons with well-controlled diabetes.

Relationship between autonomic and peripheral neuropathies and cardiovascular outcomes in diabetes

This review explores the complex relationship between diabetic neuropathy and cardiovascular disease (CVD). Neuropathy, a common complication of type 1 and type 2 diabetes, is divided into autonomic and peripheral types, each impacting cardiovascular health. Cardiovascular autonomic neuropathy, a form of autonomic neuropathy, is associated with various CVD complications, including arrhythmias, impaired nocturnal blood pressure regulation, and increased mortality. The prevalence of cardiovascular autonomic neuropathy varies depending on the type and duration of diabetes and is influenced by factors like glycemic control and metabolic stress. Peripheral polyneuropathy, which is often linked to diabetic foot disease, is also correlated with elevated CVD risk; research suggests shared pathophysiological mechanisms between peripheral neuropathy and cardiovascular conditions. Screening for neuropathies using tools like the Michigan Neuropathy Screening Instrument and heart rate variability analyses can facilitate early detection of CVD risk. Additionally, emerging technologies, like deep learning models, have demonstrated promise in detecting early cardiovascular patterns associated with autonomic neuropathy through electrocardiogram analysis. These findings underscore the value of integrating novel diagnostic approaches for early intervention. As CVD represents a leading cause of death among patients with diabetes, this article emphasizes the need for thorough assessment and proactive management of neuropathy to mitigate cardiovascular risk. The review recommends a multidisciplinary approach to diabetes care, including early screening, accurate risk stratification, and targeted therapeutic strategies to prevent or slow the progression of CVD in patients with autonomic and peripheral neuropathies. Further research is warranted to clarify the optimal intervention strategies for reducing CVD risk in these populations.

Circadian heart rate fluctuations predict 21-year cardiovascular and all-cause mortality in type 2 and type 1 diabetes

Abstract Background Alterations in circadian heart rate (HR) fluctuations have been associated with cardiovascular events in the general population. This study aimed at defining their long-term prognostic value for cardiovascular and all-cause mortality in patients with diabetes. Methods We examined a cohort of 349 patients with type 2 or type 1 diabetes (52% women, age 57.1±11.9 years, BMI 29.4±5.9 kg/m2, HbA1c 8.6±2.1%, 81% type 2 diabetes) who underwent 24h ambulatory blood pressure and HR monitoring (ABPM) and assessment of diabetic microvascular complications. The median standard deviation (SD) value of ABPM-derived HR measurements was used to define patients with low daily HR fluctuations (low 24h-HR SD), while a <10% decline in average night-time vs day-time HR identified patients with blunted nocturnal HR dip (n=107, 31%). The clinical features and time-dependent prognostic impact of these conditions were evaluated over a 21-year observational follow-up. Results Low 24h-HR SD and blunted nocturnal HR dip were associated with an adverse cardiometabolic risk profile and high prevalence of cardiac autonomic neuropathy and nephropathy. After 6,251 person-years of follow-up (21.0 [14.0-21.0] years), a total of 136 (39%) deaths occurred, of which 100 (68%) of cardiovascular cause. After adjustment for potential confounders, the low 24h-HR SD group had a higher risk for both cardiovascular (hazard ratio 1.99, 95% CI 1.29–3.06, p=0.002) and all-cause mortality (hazard ratio 1.50, 95% CI 1.03–2.18, p=0.033), compared with high 24h-HR SD. Consistently, patients with blunted nocturnal HR dip had a higher adjusted risk for cardiovascular (1.61, 95% CI 1.07–2.43, p=0.023) and all-cause mortality (1.61, 95% CI 1.11–2.34, p=0.012), compared with those with preserved nocturnal HR dip. Conclusions Impaired circadian HR fluctuations are frequent in patients with long-standing diabetes and are associated with microvascular disease and increased long-term cardiovascular and all-cause mortality. Identifying these conditions via 24h-ABPM may provide a cost-effective risk stratification tool in this high-risk population.Kaplan-Meier curves

Possible Glycemic Effects of Vagus Nerve Stimulation Evaluated by Continuous Glucose Monitoring in People with Diabetes and Autonomic Neuropathy: A Randomized, Sham-Controlled Trial.

Objective: Autonomic neuropathy is associated with dysglycemia that is difficult to control. We investigated if transcutaneous vagus nerve stimulation (tVNS) could improve glycemic levels. Methods: We randomized 145 individuals with type 1 diabetes (T1D) (n = 70) or type 2 diabetes (T2D) (n = 75) and diabetic autonomic neuropathy (DAN) to self-administered treatment with active cervical tVNS (n = 68) or sham (n = 77) for 1 week (4 daily stimulations) and 8 weeks (2 daily stimulations), separated by a wash-out period of at least 2 weeks. Continuous glucose monitoring (CGM) indices were measured for 104 participants starting 5 days prior to intervention periods, during the 1-week period, and at end of the 8-week period. Primary outcomes were between-group differences in changes in coefficient of variation (CV) and in time in range (TIR 3.9-10 mmol/L). Secondary outcomes were other metrics of CGM and HbA1c. Results: For the 1-week period, median [interquartile range] changes of CV from baseline to follow-up were -1.1 [-4.3;2.0] % in active and -1.5 [-4.4;2.5] % in sham, with no significance between groups (P = 0.54). For TIR, the corresponding changes were 2.4 [-2.1;7.4] % in active and 5.1 [-2.6;8.8] in sham group (P = 0.84). For the 8-week treatment period, changes in CV and TIR between groups were also nonsignificant. However, in the subgroup analysis, persons with T1D receiving active tVNS for 8 weeks had a significant reduction in CV compared with the T1D group receiving sham stimulation (estimated treatment effect: -11.6 [95% confidence interval -20.2;-2.0] %, P = 0.009). None of the changes in secondary outcomes between treatment groups were significantly different. Conclusions: Overall, no significant changes were observed in CGM metrics between treatment arms, while individuals with T1D and DAN decreased their CV after 8 weeks of tVNS treatment.

A Novel Pathogenic Mutation in WNK1 Gene Causing HSAN Type II in Three Siblings.

Hereditary sensory and autonomic neuropathy (HSAN) is a rare genetic disorder that primarily affects the peripheral nervous system, leading to a progressive loss of the ability to perceive pain, temperature, and touch. This condition can result in severe complications, including injuries and infections due to the inability to feel pain. HSAN is classified into nine types, with types I and VII exhibiting autosomal dominant inheritance, while the others follow an autosomal recessive pattern. In this study, we examined three affected brothers of Turkish Azeri descent, aged 20, 23, and 25 years. They presented symptoms such as a lack of temperature and pain sensation, frequent wounds and infections, self-harm, and hyperkeratosis. To identify the genetic cause of their condition, whole-exome sequencing (WES) was performed, followed by Sanger sequencing to confirm the findings. The results revealed a homozygous likely pathogenic nonsense mutation, c.2971C > T (p.Arg991Ter), in exon 9 of the WNK1 gene. This mutation results in the truncation of three isoforms of the WNK1 protein, which are essential for pain perception. This discovery enhances our understanding of HSAN and highlights the importance of genetic testing for accurate diagnosis and future screening.

Association between sebum secretion and cardiac sympathetic dysfunction in Parkinson's disease

BackgroundPatients with Parkinson's disease (PD) have α-synuclein (α-Syn) deposition in the skin, and decreased sebum secretion due to epidermal dysfunction. However, the relationship between sebum secretion and autonomic neuropathies is unknown. MethodsUsing the medical records in our facility, we identified patients newly diagnosed with PD on admission from August 2020 to December 2023. We analyzed whether sebum secretory ability at multiple sites was associated with cardiac sympathetic nerve function that was assessed by cardiac 123I-metaiodobenzylguanidine scintigraphy. ResultsForty patients were included. Their sebum secretion ability positively correlated with the ratio of the average pixel count in the heart to that in the mediastinum (H/M ratio) in the posterior neck, the anterior chest, the arms, and the abdomen. In the multiple regression analysis, those in the arms (β, 8.8; 95 % CI, 4.4–13.2; P < 0.001) and abdomen (β, 1.3; 95 % CI, 0.1–2.5; P = 0.032) were associated with the H/M ratio after controlling for age, sex, and UPDRS part III. ConclusionThis study revealed an association between sebum secretion in the arms and the abdomen, and cardiac sympathetic nerve function in PD patients. The site of the sebum secretory disturbance associated with cardiac sympathetic nerves closely resembled the gradient of α-Syn deposition in the skin, corroborating its deposition pattern. Our findings suggest that noninvasive sebum measurement may serve as an adjunctive diagnostic tool of α-Syn deposition in the skin for PD and provide insights into sympathetic nerve damage alongside cardiac sympathetic nerve assessments.

Evaluation of the Steno Type 1 Risk Engine in predicting cardiovascular events in an ethnic mixed population of type 1 diabetes mellitus and its association with chronic microangiopathy complications

BackgroundThe Steno Type 1 Risk Engine (ST1RE) was developed to aid clinical decisions in primary prevention for individuals with type 1 diabetes (T1D), as existing cardiovascular (CV) risk models for the general population and type 2 diabetes tend to underestimate CV risk in T1D. However, the applicability of ST1RE in different populations remains uncertain, as prediction models developed for one population may not accurately estimate risk in another. This study aimed to evaluate the performance of the ST1RE in predicting CV events among ethnically mixed T1D individuals and its association with the progression of microangiopathy complications.MethodsA retrospective survey of 435 adults with T1D who were free of CV events at baseline was assessed by ST1RE and chronic diabetes complications at 5 and 10 years of follow-up. The estimated CV risk rates were compared with the observed rates at 5 and 10 years using statistical analyses, including Receiver Operating Characteristic (ROC) curve analysis, Hosmer-Lemeshow test, Kaplan-Meier curves analysis and Cox-regression models.ResultsAmong 435 patients (aged 25 years; interquartile range [IQR]: 21–32) with a median T1D duration of 13 years (IQR: 9–18), only 5% were categorized into the high ST1RE group. Within a median follow-up of 9.2 years (IQR 6.0-10.7), 5.5% of patients experienced a CV event (1.6%, 14.9%, and 50% from the low, moderate, and high-risk groups, respectively). The hazard ratios (HRs) for CV events were greater in the high-risk group (HR 52.02; 95% CI 18.60–145.51, p < 0.001) and in the moderate-risk group (HR 8.66; 95% CI 2.90–25.80, p < 0.001) compared to the low-risk group. The ST1RE estimated CV events were similar to the observed at 5 years (3.4% vs. 3.5%; χ2 = 10.12, p = 0.899) and 10 years (6.8% vs. 9.9%; χ2 = 14.80, p = 0.676) of follow-up. The progression of microangiopathies was greater in the high vs. low for retinopathy (p = 0.008), diabetic kidney disease (p < 0.001), peripheral neuropathy (p = 0.021), and autonomic neuropathy (p = 0.008).ConclusionsST1RE performed well in predicting CV events at 5 and 10 years of follow-up. Moreover, higher ST1RE scores were associated with the progression of microangiopathy complications in this genetically heterogeneous T1D population.Graphical abstract

Congenital Insensitivity to Pain With Anhidrosis Is Associated With Harlequin Color Change: A Survey Study.

Congenital insensitivity to pain with anhidrosis (CIPA), also known as hereditary sensory and autonomic neuropathy (HSAN) type IV, is an extremely rare autosomal recessive congenital condition characterized by the loss of sensation to pain and absence of sweating with one case report linking this with harlequin color change. To explore the relationship further, we developed a survey using the Research Electronic Data Capture software and distributed it to families and others with close relationships and knowledge of patients with CIPA. Our results indicate that harlequin color change, characterized by unilateral flushing of the face and/or body, was significant and noted by all respondents as being present early in the condition appearing around the same time as first symptoms and around or before diagnosis of CIPA. Future clinicians should be aware of this dermatological phenomenon and its potential association with CIPA patients, especially during early disease manifestation where diagnosis can be difficult.

Immune-Mediated Neuropathies: Top 10 Clinical Pearls.

Immune-mediated neuropathies encompass a range of neurological disorders, including chronic inflammatory demyelinating polyradiculoneuropathy, Guillain-Barré syndrome, multifocal motor neuropathy, autoimmune autonomic neuropathies, and paranodal nodopathies. Recognizing clinical patterns is key to narrowing the broad range of differential diagnoses in immune-mediated neuropathies. Electrodiagnostic testing is a useful tool to support the diagnosis of immune-mediated neuropathies. Our understanding of autoimmune demyelinating neuropathies is rapidly advancing, particularly with the discovery of nodal and paranodal antibodies. Recent advances in neuropathy treatment include the utilization of neonatal Fc receptors to reduce antibody recycling, and the development of complement inhibitors to reduce inflammatory damage, offering promising new therapeutic avenues. Timely identification of immune-mediated neuropathies is imperative as delay in diagnosis and treatment may lead to irreversible disability.

Normative data on measures of cardiovascular autonomic neuropathy and the effect of pretest conditions in a large Danish non-diabetic CVD-free population from the Lolland-Falster Health Study.

Cardiovascular autonomic neuropathy (CAN) is a common diabetic complication associated with excess morbidity and mortality. CAN is also seen in conditions such as Parkinson's disease. Normative reference data for cardiovascular autonomic function are used to stratify individuals into those with and without CAN. However, reference thresholds for both cardiovascular autonomic reflex tests (CARTs) and heart rate variability (HRV) are scarce and based on small sample sizes. The aim of the study was to establish contemporary normative reference thresholds based on a large non-diabetic population free of cardiovascular disease (CVD). Cardiovascular autonomic function, CARTs and 5-min HRV indices were assessed in individuals without diabetes and CVD from the Lolland-Falster Health Study (2018-2020) by applying the point-of-care device Vagus™. Age-specific normative reference thresholds were estimated by using log-transformed quantile regression models at the 5th and 10th percentile, with adjustments made for sex. Models assessing the association between age and HRV indices were further adjusted for heart rate. We present age-specific normative reference thresholds for cardiovascular autonomic function, including CARTs and HRV, for 875 individuals (48% females) aged 15-85years. The reference thresholds are presented for both the 5th and 10th lower percentile. Higher age was inversely associated with all outcomes. Females tended to have a higher parasympathetic drive compared to males. Pre-test conditions did not affect CARTs significantly. The presented age-related normative reference thresholds for both CARTs and HRV indices based on a large Danish cohort may facilitate improved quality of research and treatment.

Low availability of haematin (hemin) in Pakistan.

Madam, Acute Intermittent Porphyria (AIP) is an autosomal dominant disorder that results from a defect in the enzyme named porphobilinogen deaminase.1 It is symptomatic porphyria, involving the accumulation of porphyrins and porphyrin precursors due to impaired conversion in haeme synthesis. Acute Intermittent Porphyria is clinically characterized by acute episodes of multiple gastrointestinal and neurologic symptoms; during which the patient remains healthy between episodes.2 Acute Intermittent Porphyria episodes are commonly observed in post pubertal females. The most common symptoms include periodic abdominal pain, vomiting and hypertension followed by neurologic damage that leads to peripheral and autonomic neuropathies (mostly motor) and psychiatric manifestations.2 Hormonal cycle regulation may worsen porphyria, since its symptoms coincide with the menstrual cycle. Although positive response has been noted in hormonal suppression by gonadotropin releasing hormone agonists.3 Currently, the most widely used treatment is hemin, a form of haeme that can be given intravenously. Its administration reduces the haeme deficit, hence limits the production of porphyrins precursors by the body. Availability of hemin in Pakistan is not promising while alternatives such as intravenous infusion of glucose, and pain relievers like Nalbuphine, a man-made opioid analgesic, and Morphine are short-term treatments. Haeme Arginate (HA), a compound of haeme and arginine, is equivalent to hematin in the treatment of AIP. Long-term weekly intravenous infusions of prophylactic HA prevent severity and frequency of porphyric attacks in patients with AIP.4 While haeme therapy is recommended if a patient exhibits neurological impairment, liver transplant appears to be the last resort in patients with recurrent clinical manifestations. To effectively mediate the growing need of Hemin in Pakistan, a systematic plan with effective and immediate steps must be introduced. The regulatory authorities must expedite the approval and licensing process of appropriate medication that would meet the growing need of the country, while not compromising on its quality. The possibility of local production should be explored, while strengthening international ties aimed at importing affordable medication. The government should focus on initiating partnerships with international organizations, non-governmental organizations (NGOs) and global health initiatives. Nationwide workshops and informative campaigns towards healthcare work should be a priority, to raise awareness of the situation and the proper steps that should be taken to minimize its adverse effects. Empowering patient advocacy groups would be beneficial in recognizing any shortcomings of the plan and to divert resources accordingly.

Improvement of heart rate variability after metabolic bariatric surgery in Korean subjects with obesity.

Cardiovascular autonomic neuropathy (CAN) is a chronic complication of diabetes. As obesity is a major risk factor for CAN, we hypothesized that metabolic bariatric surgery (MBS) could improve CAN indices in Korean patients with obesity. Patients who underwent bariatric surgery between February 2020 and June 2022 were prospectively recruited. CAN was conducted once before surgery and again after surgery, using the Ewing method and heart rate variability (HRV) analysis (standard deviation of the NN interval [SDNN], root mean square of successive RR interval difference [RMSSD], and spectral analysis). A total of 47 patients were included. The mean age was 39.8 ± 8.7 years, 15 (31.9%) were male, and 26 (55.3%) had diabetes. Resting HR before surgery was 81.0 ± 12.3 bpm, which decreased significantly to 68.0 ± 9.3 bpm after surgery (P < 0.001). Changes in HR and BP according to the Valsalva maneuver, postural changes, and handgrip were not significantly different before and after surgery. However, SDNN significantly increased from 25.2 [15.1, 33.5] to 38.0 [25.4, 45.0] ms (P < 0.001), and RMSSD also significantly increased from 17.0 [9.2, 31.8] to 28.2 [15.3, 45.6] ms (P = 0.001). Both low-frequency power (LF) and high-frequency power (HF) increased significantly, and the LF/HF ratio significantly decreased from 2.1 ± 1.6 to 1.3 ± 1.3 (P = 0.010). Loss of weight, fat mass, and lean body mass were independently associated with improving the HRV variables. MBS improved HRV variables, and these changes were mainly associated with postoperative weight loss.

Association of Continuous Glucose Monitoring-Derived Glycemia Risk Index With Cardiovascular Autonomic Neuropathy in Patients With Type 1 Diabetes Mellitus: A Cross-sectional Study.

The glycemia risk index (GRI) is a new composite continuous glucose monitoring (CGM) metric for weighted hypoglycemia and hyperglycemia. We evaluated the association between the GRI and cardiovascular autonomic neuropathy (CAN) and compared the effects of the GRI and conventional CGM metrics on CAN. For this cross-sectional study, three-month CGM data were retrospectively analyzed before autonomic function tests were performed in 165 patients with type 1 diabetes. CAN was defined as at least two abnormal results of parasympathetic tests according to an age-specific reference. The overall prevalence of CAN was 17.1%. Patients with CAN had significantly higher GRI scores, target above range (TAR), coefficient of variation (CV), and standard deviation (SD) but significantly lower time in range (TIR) than those without CAN. The prevalence of CAN increased across higher GRI zones (P for trend <.001). A multivariate logistic regression analysis, adjusted for covariates such as HbA1c, demonstrated that the odds ratio (OR) of CAN was 9.05 (95% confidence interval [CI]: 2.21-36.96, P = .002) per 1-SD increase in the GRI. TIR and CV were also significantly associated with CAN in the multivariate model. The area under the curve of GRI for the prediction of CAN (0.85, 95% CI: 0.76-0.94) was superior to that of TIR (0.80, 95% CI: 0.71-0.89, P for comparison = .046) or CV (0.71, 95% CI: 0.57-0.84, P for comparison = .049). The GRI is significantly associated with CAN in patients with type 1 diabetes and may be a better CGM metric than TIR for predicting CAN.